Affinage

PF4

Platelet factor 4 · UniProt P02776

Length
101 aa
Mass
10.8 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PF4/CXCL4 is a highly cationic, heparin-neutralizing CXC chemokine stored in platelet secretory granules whose biological output is dominated by its capacity to bind polyanions and assemble into multivalent complexes that drive immune, hematopoietic, fibrotic, and vascular responses (PMID:803847, PMID:15304392, PMID:17218382). As a foundational property, PF4 forms charge-neutralizing complexes with heparin (PMID:803847), and intact PF4 tetramers assemble with unfractionated heparin into ultralarge (>670 kDa) complexes over a narrow molar ratio that are the principal antigenic targets in heparin-induced thrombocytopenia and drive FcγRIIA-dependent platelet activation (PMID:15304392). These complexes behave as T cell-dependent antigens requiring CD4 T-cell help and CD40-dependent T-B cooperation (PMID:15845897, PMID:25595736), and the resulting PF4/heparin antibodies propagate thrombotic signaling by inducing monocyte tissue factor via FcγRI-MEK1-ERK1/2 (PMID:22394597), engaging FcγRIIA on neutrophils bound to surface chondroitin sulfate (PMID:18539895), and triggering classical-pathway complement activation through polyreactive natural IgM (PMID:30309891); PF4 itself also activates platelets directly by binding the thrombopoietin receptor c-Mpl, activating JAK2 and STAT3/STAT5 (PMID:37883794). Beyond complex formation, secreted PF4 acts through multiple cell-surface platforms: cell-surface glycosaminoglycans and chondroitin sulfate proteoglycans (PMID:19910578, PMID:18539895, PMID:36640356), integrins αvβ3/αvβ5/α5β1 on endothelium where soluble PF4 inhibits adhesion and angiogenesis (PMID:18648521, PMID:34099640), the GPCRs CXCR3 and CCR1 (PMID:16337473, PMID:29930254), and CD36 on macrophages (PMID:30169632). Through these receptors PF4 reprograms myeloid cells—downregulating CD163 on macrophages (PMID:19910578), driving monocyte survival and cytokine output via sphingosine kinase 1 (PMID:20104488), and synergizing with TLR8 to activate TBK1/IKKε-IRF5 and the NLRP3 inflammasome (PMID:35701499)—and organizes self- and microbial DNA and RNA into liquid-crystalline complexes that amplify TLR9 and TLR7/8 responses in dendritic cells, a mechanism central to systemic sclerosis pathology (PMID:31043596, PMID:36614095). PF4 is a potent pro-fibrotic effector, directly inducing myofibroblast differentiation and collagen synthesis and promoting fibrosis across skin, lung, heart, and liver (PMID:34986347, PMID:20162727), partly via monocyte-derived PDGF-BB (PMID:32284212). As a megakaryocyte- and platelet-derived niche factor it enforces HSC quiescence and supports HSC self-renewal (PMID:25326802, PMID:27222476). Megakaryocytic PF4 transcription is directly controlled by RUNX1 and by USF1/USF2 acting on E-box/TME promoter elements (PMID:21129147, PMID:15187018).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1975 Medium

    Established PF4's defining biochemical identity as a heparin-neutralizing platelet protein, framing all later polyanion-driven mechanisms.

    Evidence Purification from human platelets with immunoelectrophoresis, heparin-neutralization assay, and trypsin digestion

    PMID:803847

    Open questions at the time
    • No structural basis for tetramerization or heparin binding defined
    • Cellular receptors not yet identified
  2. 1989 Medium

    Showed PF4 has lineage-specific autoregulatory effects on its own producer lineage, inhibiting megakaryocyte maturation.

    Evidence Megakaryocyte colony formation assays, in situ hybridization for Factor V mRNA, COOH-terminal peptide mapping

    PMID:2523411

    Open questions at the time
    • Receptor mediating the inhibition not identified
    • Relationship to later HSC quiescence role unestablished
  3. 2000 High

    Identified MMP-9 as a protease that degrades PF4, distinguishing its regulation from other chemokines and indicating proteolytic turnover.

    Evidence In vitro proteolysis assay with purified neutrophil progelatinase B activated by stromelysin-1

    PMID:11023497

    Open questions at the time
    • Cleavage sites and biological consequences of fragments not defined
  4. 2004 High

    Defined the molecular requirements for the antigenic PF4/heparin complex in HIT, explaining why only certain heparins and intact tetramers are pathogenic.

    Evidence Electron microscopy, size-exclusion chromatography, PF4 tetramerization mutagenesis, platelet activation and antibody-binding assays; plus identification of USF1/USF2 transcriptional control

    PMID:15187018 PMID:15304392

    Open questions at the time
    • Structural model of ultralarge complex not resolved
    • Determinants of the conformational neoepitope not fully mapped
  5. 2005 Medium

    Established that PF4/heparin complexes are T cell-dependent antigens and revealed receptor-specific opposing effects on T helper differentiation via CXCR3 isoforms.

    Evidence Euthymic vs athymic mouse immunization; T-cell line cytokine, promoter, and CXCR3-blocking assays

    PMID:15845897 PMID:16337473

    Open questions at the time
    • CXCR3-A vs CXCR3-B signaling divergence shown in single laboratory
    • In vivo relevance of TH2 skewing not established
  6. 2007 High

    Distinguished regulated, PKC-dependent secretion of CXCL4 from constitutive secretion of its variant CXCL4L1, defining how PF4 release is controlled.

    Evidence Transfection of multiple cell types, subcellular fractionation, PKC stimulation and secretion assays

    PMID:17218382

    Open questions at the time
    • Granule sorting determinants not identified
  7. 2010 Medium

    Connected PF4 to organ fibrosis and dissected myeloid signaling, showing genetic deletion reduces liver fibrosis and that PF4 modulates monocyte chemokine receptors and survival pathways.

    Evidence Cxcl4−/− mice in two liver injury models; monocyte CCR downregulation via autocrine TNF-α; SphK1 enzyme/translocation/siRNA studies; CXCR3-dependent microglial migration

    PMID:18248618 PMID:20104488 PMID:20162727 PMID:21088050

    Open questions at the time
    • Direct fibroblast receptor for PF4 not identified at this stage
    • SphK1 and TNF-α pathways each from single laboratory
  8. 2011 High

    Identified RUNX1 as a direct transcriptional driver of PF4 in megakaryocytes and outlined the dual CXCR3-B/proteoglycan signaling architecture.

    Evidence ChIP, EMSA, reporter mutagenesis, RUNX1 knockdown/overexpression; synthesis of CXCR3-B (Gs/cAMP/p38) and proteoglycan (Src/Syk/Rac2/SphK1) signaling

    PMID:21129147 PMID:21295372

    Open questions at the time
    • Signaling synthesis aggregates components from disparate single studies
    • Interplay between transcriptional regulators not fully mapped
  9. 2012 High

    Provided a mechanism for HIT thrombosis by showing antibody complexes drive monocyte tissue factor expression through FcγRI and MEK1-ERK1/2.

    Evidence Ex vivo monocyte stimulation with KKO and patient plasma, TF and microparticle assays, FcγRI blocking, MEK inhibition

    PMID:22394597

    Open questions at the time
    • Relative contributions of monocyte vs platelet procoagulant activity in vivo not quantified
  10. 2014 High

    Identified megakaryocyte-derived CXCL4 as a niche signal enforcing HSC quiescence, linking platelet biology to stem cell regulation.

    Evidence In vivo CXCL4 injection, Cxcl4−/− mice, MK depletion, 3D whole-mount imaging; plus CXCR3/p38-p53-Bax apoptotic cascade in intestinal epithelium

    PMID:24800927 PMID:25326802

    Open questions at the time
    • HSC receptor for CXCL4 quiescence signal not defined
    • Reconciliation of quiescence-promoting vs self-renewal roles incomplete
  11. 2016 High

    Demonstrated an autocrine/paracrine requirement for CXCL4 in HSPC survival and self-renewal, complementing the niche quiescence role.

    Evidence siRNA knockdown in human CD34+ cells, Cxcl4−/− mice, serial transplantation, colony assays

    PMID:27222476

    Open questions at the time
    • CXCR2 mechanistic role in HSPCs not fully resolved
  12. 2018 High

    Expanded the PF4 receptor repertoire and innate-immune amplifying functions: CCR1 agonism for monocyte chemotaxis and TLR8 synergy driving inflammasome and enhancer remodeling.

    Evidence Chemotaxis/calcium/PTX/chondroitinase/CCR1-transfectant assays; kinase, IRF5, NLRP3, and ATAC/ChIP epigenomic profiling; CD4 T-cell/CD40 dependence of antibody production

    PMID:25595736 PMID:29930254 PMID:35701499

    Open questions at the time
    • How GAG presentation couples to CCR1 activation not structurally defined
    • Endogenous TLR8 ligand context in vivo not established
  13. 2019 High

    Defined PF4 as a nucleic-acid-organizing scaffold that amplifies TLR9 responses, and mapped its heterodimerization with CXCL12 controlling cancer cell migration.

    Evidence Biophysical liquid-crystalline complex assays, pDC stimulation, CXCR3-independence; NMR interface mapping with CXCL12 and migration assays; CD36-dependent macrophage phagocytosis post-MI

    PMID:30169632 PMID:31043596 PMID:31785332

    Open questions at the time
    • Receptor sensing the liquid-crystalline complex beyond endosomal TLR9 not defined
    • CD36 mechanism shown in single laboratory
  14. 2022 High

    Established PF4 as a direct pro-fibrotic effector across multiple organs and dissected the monocyte-PDGF-BB and CIITA/DC reprogramming routes to fibrosis.

    Evidence Cxcl4−/− and human CXCL4 overexpression mice in multiple fibrotic models, blocking, in vitro myofibroblast differentiation; PDGF-BB and CIITA pathway dissection

    PMID:32284212 PMID:33042127 PMID:34986347

    Open questions at the time
    • Direct fibroblast/endothelial receptor mediating myofibroblast differentiation not identified
    • PDGF-BB and CIITA routes each from single laboratory
  15. 2023 Medium

    Resolved how endothelial GAG sulfation tunes PF4-driven, receptor-independent leukocyte recruitment, extended nucleic-acid sensing to RNA, and revealed a beneficial neurogenic exerkine role.

    Evidence Biophysical GAG-binding/mutant studies with leukocyte adhesion and permeability assays; CXCL4-RNA RNase protection and TLR7/8-dependent DC stimulation; platelet depletion and CXCL4 injection in aged mice

    PMID:36614095 PMID:36640356 PMID:37587147

    Open questions at the time
    • Receptor for hippocampal neurogenic effect not identified
    • RNA-complex mechanism from single laboratory
  16. 2024 High

    Identified c-Mpl/JAK2 as a direct PF4 platelet-activating receptor axis, unifying VITT and HIT platelet activation through dual FcγRIIA and c-Mpl engagement.

    Evidence PF4-c-Mpl binding, JAK2/STAT3/STAT5 phosphorylation, pathway inhibition, platelet aggregation with VITT sera and patient IgG

    PMID:37883794

    Open questions at the time
    • Structural basis of PF4 binding to c-Mpl not resolved
    • Relative contribution of c-Mpl vs FcγRIIA in vivo not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct cell-surface receptor(s) mediating PF4-induced myofibroblast differentiation, HSC quiescence, and neuro-regenerative effects remain unidentified, and a unified structural model linking polyanion-complex assembly to the distinct receptor systems is lacking.
  • No defined receptor for the direct pro-fibrotic effect
  • No structural model connecting tetramer/complex states to integrin, CXCR3, CCR1, c-Mpl, and CD36 engagement
  • Endogenous physiological versus pathological balance of PF4 functions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 2 GO:0031012 extracellular matrix 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-109582 Hemostasis 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
CCR1CD36CXCL12CXCR3FCGR2AITGAVITGB3MPL

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 PF4 tetramers and unfractionated heparin form ultralarge complexes (>670 kDa) over a narrow molar ratio (~1:1 PF4:heparin); these ultralarge complexes are more reactive toward HIT-like monoclonal antibodies and promote greater FcγRIIA-dependent platelet activation than smaller complexes. Formation of ultralarge complexes required intact PF4 tetramers (demonstrated by mutation studies) and did not occur with low-molecular-weight heparin or fondaparinux. Electron microscopy, size-exclusion chromatography, mutagenesis of PF4 tetramerization, platelet activation assays, antibody-binding assays Blood High 15304392
2000 Neutrophil gelatinase B (MMP-9) degrades PF4 (platelet factor 4), in contrast to its potentiating effect on IL-8; PF4 is thus a substrate of MMP-9 proteolysis. In vitro proteolysis assay with purified human neutrophil progelatinase B activated by stromelysin-1; gel analysis of cleavage products Blood High 11023497
2014 Megakaryocytes are the predominant source of CXCL4 in the bone marrow niche; CXCL4 secreted by megakaryocytes directly regulates HSC quiescence. In vivo CXCL4 injection increased HSC quiescence and reduced HSC number, while Cxcl4−/− mice showed increased HSC number and proliferation. 3D whole-mount imaging confirmed HSCs are preferentially located adjacent to megakaryocytes. In vivo CXCL4 injection, Cxcl4−/− mouse model, selective MK depletion, 3D whole-mount imaging, gene expression analysis, flow cytometry Nature medicine High 25326802
2007 CXCL4 is stored in secretory granules and released in response to protein kinase C (PKC) activation, whereas its non-allelic variant CXCL4L1 is continuously secreted via a constitutive pathway. This difference in subcellular localization and regulated secretion was established in multiple transfected cell types and confirmed in lymphocytes (primarily CXCL4) and smooth muscle cells (primarily CXCL4L1). Transfection of multiple cell types, subcellular fractionation/localization, PKC stimulation assays, secretion pathway analysis Blood High 17218382
2011 RUNX1 is a direct transcriptional regulator of the PF4 gene. RUNX1 binds to consensus sites at −1774/−1769 and −157/−152 on the PF4 promoter. Mutation of either site markedly reduced promoter activity; RUNX1 knockdown decreased and RUNX1 overexpression increased PF4 promoter activity and protein levels. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), luciferase reporter assay, siRNA knockdown, RUNX1 overexpression in HEL cells Journal of thrombosis and haemostasis High 21129147
2004 Upstream stimulatory factors USF1 and USF2 bind E-box motifs in the TME regulatory element of the PF4 promoter and strongly transactivate PF4 expression in megakaryocytic cells; physiological binding of USF1/2 to the TME in rat megakaryocytes was confirmed. Mass spectrometry identification of promoter-binding proteins, ChIP assay in primary megakaryocytes, luciferase reporter assay, EMSA, RT-PCR Blood High 15187018
2019 CXCL4 organizes self-DNA and microbial DNA into liquid crystalline immune complexes that amplify TLR9-mediated plasmacytoid dendritic cell hyperactivation and interferon-α production. This activity does not require CXCR3. CXCL4-DNA complexes were detected in vivo in SSc blood and correlated with the type I IFN signature. Biophysical characterization (liquid crystalline complex formation), in vitro pDC stimulation assays, CXCR3 blocking/knockout experiments, detection of complexes in patient plasma, skin pDC immunostaining Nature communications High 31043596
2009 CXCL4 directly downregulates CD163 (hemoglobin-haptoglobin scavenger receptor) expression on human macrophages differentiated from monocytes, resulting in inability to upregulate heme oxygenase-1 in response to hemoglobin-haptoglobin complexes. CXCL4's effect was neutralized by heparin (which binds CXCL4) and blocked by chlorate pretreatment (inhibiting glycosaminoglycan synthesis), indicating CXCL4 acts through cell-surface glycosaminoglycans. Flow cytometry, mRNA quantification (time-course), heparin neutralization, chlorate inhibition of GAG synthesis, platelet releasate experiments, immunofluorescence of human plaques Circulation research High 19910578
2018 CXCL4 is an agonist of CCR1 and drives chemotaxis of primary human monocytes through CCR1. CXCL4-induced migration and calcium responses in THP-1 cells were pertussis toxin-sensitive (implying Gi-coupled GPCR), abrogated by chondroitinase ABC (requiring cell-surface GAG presentation), insensitive to CXCR3 antagonist, and inhibited by a CCR1 antagonist. CXCL4 also induced CCR1 endocytosis. Chemotaxis assays, intracellular calcium measurements, pertussis toxin treatment, chondroitinase ABC treatment, CCR1-transfectant migration assays, CCR1 endocytosis assay, CCR1 antagonist inhibition Scientific reports High 29930254
2005 CXCL4 and CXCL10 exert opposite effects on human TH1/TH2 cytokine production via their respective interactions with CXCR3-B and CXCR3-A. CXCL4 downregulates IFN-γ and upregulates TH2 cytokines (IL-4, IL-5, IL-13), downregulates T-bet, upregulates GATA-3, and induces direct activation of IL-5 and IL-13 promoters. These effects were blocked by anti-CXCR3 antibody. Quantitative RT-PCR, flow cytometry, ELISA on antigen-specific and polyclonally activated T-cell lines, anti-CXCR3 blocking antibody, IL-5/IL-13 promoter activation assays The Journal of allergy and clinical immunology Medium 16337473
2008 CXCL4 interacts with αvβ3, αvβ5, and α5β1 integrins on human endothelial cells. Immobilized CXCL4 supports endothelial cell adhesion, spreading, and migration in an integrin-dependent manner, whereas soluble CXCL4 inhibits integrin-dependent adhesion and migration, contributing to its anti-angiogenic effect. Cell adhesion assays with integrin-transfected CHO cells, HUVEC adhesion/spreading/migration assays, integrin-blocking antibodies PloS one Medium 18648521
2008 CXCL4 binds to chondroitin sulfate proteoglycans on neutrophil surfaces; immune complexes of PF4 and anti-PF4 antibodies colocalize with CD32a (FcγRIIA) on neutrophils and activate neutrophils (~3-fold increase in Mac-1 expression, degranulation, enhanced adhesion). Chondroitinase ABC treatment blocked PF4 binding and cell activation. Arginine 49 of PF4 was identified as important for stabilizing PF4-chondroitin binding. Flow cytometry, confocal microscopy, chondroitinase ABC treatment, anti-CD32/FcγRII blocking antibody, recombinant PF4 mutagenesis (Arg49), degranulation assays, cell adhesion assays Blood High 18539895
2012 PF4/heparin antibody complexes induce monocyte tissue factor (TF) expression and release of TF-positive microparticles via engagement of FcγRI receptor and activation of the MEK1-ERK1/2 signaling pathway, providing a mechanism for thrombosis in HIT. Ex vivo monocyte stimulation with monoclonal anti-PF4/heparin antibody (KKO) and HIT patient plasma, TF expression assays, microparticle quantification, FcγRI blocking, MEK1-ERK1/2 pathway inhibition Blood High 22394597
2005 PF4/heparin complexes are T cell-dependent antigens. Euthymic mice immunized with mPF4/heparin complexes (but not mPF4 or heparin alone) developed heparin-dependent autoantibodies with HIT-like characteristics; athymic mice did not develop these antibodies. Murine immunization model, euthymic vs. athymic mice comparison, platelet activation assay, antibody binding assays Blood High 15845897
2015 CD4 T cells are required for production of PF4/heparin-specific antibodies. Depletion of CD4 T cells markedly impaired PF4/heparin-specific antibody induction; reconstitution experiments showed T-cell help is necessary; B cells lacking CD40 showed markedly reduced PF4/heparin-specific antibody production, demonstrating CD40-dependent T-B cell cooperation. CD4 T-cell depletion with anti-CD4 antibody, Rag1−/− reconstitution with B cells ± T cells, B cell-specific CD40 knockout mice, ELISA for specific antibodies Blood High 25595736
2011 CXCL4 signaling via CXCR3-B activates Gs proteins, elevates cAMP, and activates p38 MAP kinase. Signaling via chondroitin sulfate proteoglycans involves Src family kinases, Syk, monomeric GTPases (including Rac2), sphingosine kinase 1, and MAP kinase family members, with biphasic kinetics of Rac2 and SphK1 activation in monocytes and neutrophils. Pharmacological inhibitors, kinase activation assays, receptor-specific experiments (CXCR3-B vs. proteoglycan), review/synthesis of multiple experimental studies European journal of cell biology Medium 21295372
2010 CXCL4 induces down-regulation of CC chemokine receptors CCR1, CCR2, and CCR5 on human monocytes through autocrine/paracrine TNF-α release; TNF-α then induces CCL3 and CCL4 secretion (desensitizing CCR1 and CCR5), while CCL2 secretion was TNF-α-independent. This limits monocyte chemotactic migration toward cognate CC chemokine ligands. Flow cytometry for CCR expression, TNF-α neutralization, chemotaxis assays, cytokine measurements, conditioned medium experiments Innate immunity Medium 21088050
2010 Sphingosine kinase 1 (SphK1) is a central regulator of CXCL4-induced monocyte survival, cytokine expression, and oxygen radical formation. CXCL4 upregulates SphK1 mRNA, induces SphK1 enzyme activity, and causes its translocation to the cell membrane. Pharmacological SphK inhibition and SphK1-specific siRNA reversed CXCL4-induced monocyte survival, cytokine expression, and ROS release; the anti-apoptotic effect involves SphK1-dependent caspase inhibition and Erk activation. SphK activity assay, SphK1 membrane translocation assay, pharmacological SphK inhibitor, siRNA knockdown, apoptosis/caspase assays, cytokine and ROS measurements European journal of immunology Medium 20104488
2009 CXCL4 protects the antimicrobial peptide LL-37 from cleavage by mast cell beta-tryptase. CXCL4 does not directly inhibit beta-tryptase but destabilizes active tetrameric beta-tryptase by antagonizing the heparin component required for tetramer integrity, thereby acting as a counter-regulator of tryptase activity. In vitro protease cleavage assays, inhibitor studies, comparison of tryptase tetramer stability, bactericidal/functional assays of LL-37 fragments Journal of immunology Medium 19625657
2008 Brain microglia express CXCL4 in vitro and in vivo under neurodegenerating conditions. CXCL4-induced microglial migration is absent in CXCR3-deficient microglia, indicating CXCR3 mediates this response. CXCL4 also attenuates LPS-induced microglial phagocytosis and nitric oxide production. In vitro microglia culture, CXCR3−/− microglia migration assays, in vivo immunohistochemistry, phagocytosis and NO production assays Journal of neurochemistry Medium 18248618
2015 Platelet secretion of CXCL4 in sepsis is Rac1-dependent. Rac1 inhibitor NSC23766 decreased CLP-enhanced plasma CXCL4 by 77% and abolished PAR4 agonist-induced CXCL4 secretion from isolated platelets. CXCL4 promotes neutrophil accumulation in the lung indirectly by inducing CXCL2 production from alveolar macrophages; CXCL4 itself did not directly drive neutrophil chemotaxis in vitro. Murine CLP sepsis model, Rac1 inhibitor, platelet depletion, ELISA for CXCL4/CXCL2, CXCR2 antagonist, in vitro neutrophil chemotaxis assay, alveolar macrophage stimulation British journal of pharmacology Medium 26478565
2021 C5a activation of C5aR1 on platelets drives preferential release of CXCL4 as an antiangiogenic effector molecule. Platelet-specific deletion of C5aR1 produced a proangiogenic phenotype; interfering with the C5aR1-CXCL4 axis reversed the antiangiogenic effect of platelets both in vitro and in vivo. C5ar1−/− mice, platelet-specific C5aR1 deletion, in vitro endothelial cell migration and tube formation assays, in vivo vascularization models, CXCL4 measurement Nature communications High 34099640
2023 CXCL4 binds glycosaminoglycan (GAG) sugars on proteoglycans within the endothelial extracellular matrix, resulting in increased leukocyte adhesion, increased vascular permeability, and non-specific recruitment of a range of leukocytes independent of classical chemokine receptors. GAG sulfation confers selectivity onto chemokine localization. Biophysical binding assays, in vitro leukocyte adhesion and vascular permeability assays, in vivo leukocyte recruitment, GAG-binding mutants Cell reports High 36640356
2018 In human monocytes/macrophages, costimulation by CXCL4 and TLR8 synergistically activates TBK1 and IKKε, repurposes these kinases toward inflammatory response via coupling with IRF5, and activates the NLRP3 inflammasome. CXCL4 + TLR8 costimulation induces chromatin remodeling and activates de novo enhancers associated with inflammatory genes, selectively amplifying IL-1β production while partially attenuating the interferon response. Kinase activation assays (TBK1, IKKε), IRF5 coupling assays, NLRP3 inflammasome activation, epigenomic profiling (ATAC-seq/ChIP), gene expression analysis, IL-1β ELISA Nature communications High 35701499
2024 PF4 binds and activates the thrombopoietin receptor c-Mpl on platelets, leading to JAK2 activation and phosphorylation of STAT3 and STAT5, resulting in platelet aggregation. Inhibition of the c-Mpl-JAK2 pathway inhibits platelet aggregation induced by PF4 alone, VITT sera, and PF4 combined with VITT IgG. PF4-based immune complexes activate platelets through both FcγRIIA (Fc domain) and c-Mpl (PF4 domain). Binding assays (PF4 to c-Mpl), JAK2/STAT3/STAT5 phosphorylation assays, c-Mpl-JAK2 pathway inhibition, platelet aggregation assays with VITT sera and patient IgG Blood High 37883794
2019 CXCL4 forms heterodimers with CXCL12; the CXCL4-CXCL12 binding interface was identified by NMR spectroscopy. CXCL4-CXCL12 heterodimers inhibit CXCL12-driven breast cancer cell migration via CXCR4. A CXCL4-derived peptide mimicking the binding interface reproduced this inhibitory activity. NMR spectroscopy (binding interface mapping), cell migration assays (MDA-MB-231), CXCR4 blocking, CXCL4-derived peptide functional assay Cellular signalling Medium 31785332
1989 PF4 inhibits human megakaryocytopoiesis in vitro with lineage specificity (no effect on myeloid or erythroid colony formation). Inhibition was mediated through impeding megakaryocyte maturation rather than proliferation. A synthetic 24-residue COOH-terminal PF4 peptide reproduced this effect and decreased Factor V mRNA expression in individual megakaryocytes (~60% reduction). Megakaryocyte colony formation assay, cell maturation analysis, in situ hybridization for Factor V mRNA in single cells, comparison with beta-thromboglobulin peptides The Journal of clinical investigation Medium 2523411
2016 CXCL4 and CXCR2 regulate survival and self-renewal of hematopoietic stem/progenitor cells. CXCL4 knockdown in human CD34+ cells significantly decreased viability and colony-forming potential. Cxcl4−/− mice showed decreased HSC numbers and reduced self-renewal capacity after secondary transplantation, demonstrating an autocrine/paracrine role of CXCL4 in HSC maintenance. siRNA knockdown in human CD34+ cells, Cxcl4−/− mouse model, serial transplantation assays, flow cytometry for HSC subpopulations, colony formation assays Blood High 27222476
2018 Polyreactive natural IgM initiates complement activation by PF4/heparin complexes through the classical complement pathway. Plasma IgM levels correlated with complement activation (r=0.898). IgM depletion abrogated C3c generation. Monoclonal polyreactive IgM and cord blood IgM generated C3c in the presence of PF4/heparin. Anti-C1q antibody prevented IgM-mediated complement activation, confirming classical pathway involvement. Proteomic correlation analysis, IgM depletion experiments, cord blood IgM, monoclonal polyreactive IgM, anti-C1q blocking, C3c generation assay, B-cell deposition assay Blood High 30309891
2010 Cxcl4 genetic deletion in mice significantly reduced liver fibrosis after CCl4 and thioacetamide-induced chronic injury, decreased infiltration of neutrophils and CD8+ T cells, and was associated with changes in fibrosis-related gene expression (Timp-1, Mmp9, Tgf-β, IL-10). In vitro, recombinant Cxcl4 stimulated proliferation, chemotaxis, and chemokine expression of hepatic stellate cells. Cxcl4−/− mice in two injury models, histological/biochemical analysis, FACS for infiltrating immune cells, in vitro hepatic stellate cell assays, gene expression analysis Hepatology High 20162727
2022 CXCL4 directly induces myofibroblast differentiation and collagen synthesis in fibroblast precursors and endothelial cells (through endothelial-to-mesenchymal transition). CXCL4-deficient mice showed reduced fibrosis in skin, lungs, and heart; overexpressing human CXCL4 in mice aggravated bleomycin-induced fibrosis; blocking CXCL4 reduced fibrosis. Cxcl4−/− mice (multiple fibrotic models), human CXCL4 overexpression mouse model, CXCL4 blocking, in vitro myofibroblast differentiation and collagen synthesis assays, single-cell ligand-receptor analysis Cell reports High 34986347
2014 CXCL4 activates the p38-MAPK pathway through CXCR3, leading to upregulation of p53 and Bax and subsequent caspase-8, -9, and -3 activation in intestinal epithelial cells (IEC-6), mediating 5-FU-induced intestinal apoptosis. Neutralizing anti-CXCL4 antibody reduced p53 and Bax expression and crypt epithelial apoptosis in vivo. In vivo 5-FU mucositis mouse model, anti-CXCL4 neutralizing antibody, in vitro IEC-6 signaling (p38-MAPK phosphorylation, p53/Bax expression, caspase activation), CXCR3 receptor identification Cancer biology & therapy Medium 24800927
2023 CXCL4 assembles RNA (in addition to DNA) into complexes that protect RNA from enzymatic degradation and persist in vivo in SSc plasma. CXCL4-RNA complexes stimulate monocyte-derived DCs to produce TNF-α, IL-12, IL-23, IL-8, and pro-collagen in a predominantly TLR7/8-dependent, CXCR3-independent manner. CXCL4-RNA complex detection in SSc patient plasma, RNase protection assays, in vitro MDDC stimulation, TLR7/8 blocking, CXCR3 blocking, cytokine/collagen measurement International journal of molecular sciences Medium 36614095
2022 CXCL4 links inflammation to fibrosis by reprogramming monocyte-derived dendritic cells through key transcriptional regulator CIITA. Inhibition of CIITA mimicked CXCL4's pro-inflammatory/pro-fibrotic phenotype. CXCL4-exposed dendritic cells produce extracellular matrix molecules and induce myofibroblast differentiation. Transcriptomic and methylation profiling (65 longitudinal profiles), gene regulatory network analysis, CIITA inhibition, in vitro myofibroblast differentiation assay, ECM production measurement Frontiers in immunology Medium 33042127
2020 CXCL4 production by pDCs in SSc is driven by simultaneous exposure to hypoxia and TLR9 activation, dependent on mitochondrial reactive oxygen species (mtROS) overproduction leading to stabilization of HIF-2α. Blocking either mtROS or HIF-2α pathways attenuated CXCL4 production. pDC culture under hypoxia ± TLR agonists, mtROS inhibition, HIF-1α/HIF-2α expression and stabilization assays (ELISA, qPCR, FACS, Western blot), umbilical cord CD34-derived pDC validation Rheumatology (Oxford) Medium 34559222
2020 CXCL4 triggers monocytes and macrophages to produce PDGF-BB, which then activates dermal fibroblasts to produce extracellular matrix and inflammatory mediators. This indirect fibroblast activation was abrogated by PDGF-receptor inhibition (Crenolanib or siRNA). TLR ligands, IFNα, and TGFβ did not induce PDGF-BB release in contrast to CXCL4. Multiplex immunoassay for cytokines, PDGF-BB quantification (immunoassay, Western blot), siRNA PDGF-receptor knockdown, Crenolanib inhibition, fibroblast ECM and cytokine production assays Journal of autoimmunity Medium 32284212
2019 CXCL4 infusion impaired macrophage phagocytic capacity by reducing CD36 levels through MMP-9-dependent and -independent signaling, leading to higher post-MI mortality and LV dilation. In vitro, a CD36 neutralizing antibody inhibited phagocytosis similarly to CXCL4, and combination of CXCL4 + CD36Ab had no additive effect, establishing CXCL4 acts through CD36 signaling. In vivo CXCL4 mini-pump infusion post-MI, echocardiography, ex vivo and in vitro phagocytosis assays, CD36 neutralizing antibody, MMP-9 measurement, gene expression analysis Cardiovascular research Medium 30169632
1975 PF4 (platelet factor 4) is a heat-stable heparin-neutralizing protein purified from human platelets; its antiheparin activity and antigenicity are destroyed by trypsin; PF4 forms a complex with heparin that shifts its electrophoretic migration from cathodal to anodal, indicating charge neutralization. SDS-PAGE, immunodiffusion, immunoelectrophoresis with monospecific antibody, heparin-neutralization assay, trypsin digestion, antibody inhibition of antiheparin activity Blood Medium 803847
2023 Platelets are activated by exercise and are required for exercise-induced hippocampal precursor cell proliferation in aged mice. The platelet-derived exerkine CXCL4/PF4 ameliorates age-related regenerative and cognitive impairments in a hippocampal neurogenesis-dependent manner when administered systemically. Platelet depletion during exercise, aged mouse model, hippocampal precursor cell proliferation assay, systemic CXCL4 injection, hippocampal neurogenesis-dependent cognitive testing Nature communications Medium 37587147

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-alpha and leaves RANTES and MCP-2 intact. Blood 546 11023497
2014 Megakaryocytes regulate hematopoietic stem cell quiescence through CXCL4 secretion. Nature medicine 484 25326802
2013 Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis. The New England journal of medicine 369 24350901
2008 Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassays. Journal of thrombosis and haemostasis : JTH 266 18489711
2012 Macrophage Phenotype Modulation by CXCL4 in Atherosclerosis. Frontiers in physiology 242 22275902
2023 Platelet-instructed SPP1+ macrophages drive myofibroblast activation in fibrosis in a CXCL4-dependent manner. Cell reports 231 36807143
2004 Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia. Blood 223 15304392
2012 VEGF, PF4 and PDGF are elevated in platelets of colorectal cancer patients. Angiogenesis 186 22402885
1996 Pathogenicity of IgA and/or IgM antibodies to heparin-PF4 complexes in patients with heparin-induced thrombocytopenia. British journal of haematology 168 8616093
2009 Role of the platelet chemokine platelet factor 4 (PF4) in hemostasis and thrombosis. Thrombosis research 147 20004006
2009 CXCL4 downregulates the atheroprotective hemoglobin receptor CD163 in human macrophages. Circulation research 140 19910578
1989 Inhibition of human megakaryocytopoiesis in vitro by platelet factor 4 (PF4) and a synthetic COOH-terminal PF4 peptide. The Journal of clinical investigation 140 2523411
2010 CXC chemokine ligand 4 (Cxcl4) is a platelet-derived mediator of experimental liver fibrosis. Hepatology (Baltimore, Md.) 136 20162727
2021 Frequency of positive anti-PF4/polyanion antibody tests after COVID-19 vaccination with ChAdOx1 nCoV-19 and BNT162b2. Blood 122 33988688
2019 CXCL4 assembles DNA into liquid crystalline complexes to amplify TLR9-mediated interferon-α production in systemic sclerosis. Nature communications 122 31043596
2015 Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early stage of rheumatoid arthritis. Annals of the rheumatic diseases 108 25858640
2023 Platelet-derived exerkine CXCL4/platelet factor 4 rejuvenates hippocampal neurogenesis and restores cognitive function in aged mice. Nature communications 103 37587147
2014 CXCL4-induced plaque macrophages can be specifically identified by co-expression of MMP7+S100A8+ in vitro and in vivo. Innate immunity 91 24663337
2005 CXCR3-mediated opposite effects of CXCL10 and CXCL4 on TH1 or TH2 cytokine production. The Journal of allergy and clinical immunology 91 16337473
2012 PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of FcγRI. Blood 89 22394597
2020 Increased CXCL4 expression in hematopoietic cells links inflammation and progression of bone marrow fibrosis in MPN. Blood 86 32726410
2017 CXCL4-induced macrophages in human atherosclerosis. Cytokine 86 28899579
2011 CXCL4 and CXCL10 predict risk of fatal cerebral malaria. Disease markers 85 21508508
2008 Immune complexes formed following the binding of anti-platelet factor 4 (CXCL4) antibodies to CXCL4 stimulate human neutrophil activation and cell adhesion. Blood 75 18539895
2018 CXCL4/Platelet Factor 4 is an agonist of CCR1 and drives human monocyte migration. Scientific reports 74 29930254
2013 Autocrine CCL2, CXCL4, CXCL9 and CXCL10 signal in retinal endothelial cells and are enhanced in diabetic retinopathy. Experimental eye research 73 23352833
2010 Interaction of PF4 (CXCL4) with the vasculature: a role in atherosclerosis and angiogenesis. Thrombosis and haemostasis 70 20806113
2008 Expression of CXCL4 in microglia in vitro and in vivo and its possible signaling through CXCR3. Journal of neurochemistry 70 18248618
2022 CXCL4 drives fibrosis by promoting several key cellular and molecular processes. Cell reports 65 34986347
2012 Lineage tracing of Pf4-Cre marks hematopoietic stem cells and their progeny. PloS one 64 23300543
2016 CXCR2 and CXCL4 regulate survival and self-renewal of hematopoietic stem/progenitor cells. Blood 61 27222476
2023 Anti-PF4 immunothrombosis without proximate heparin or adenovirus vector vaccine exposure. Blood 59 37883798
2021 Platelet CXCL4 mediates neutrophil extracellular traps formation in ANCA-associated vasculitis. Scientific reports 57 33420306
2011 Molecular pathways of platelet factor 4/CXCL4 signaling. European journal of cell biology 56 21295372
2022 Platelet-activating anti-PF4 disorders: An overview. Seminars in hematology 55 35512902
2007 PF-4/CXCL4 and CXCL4L1 exhibit distinct subcellular localization and a differentially regulated mechanism of secretion. Blood 55 17218382
2019 Exogenous CXCL4 infusion inhibits macrophage phagocytosis by limiting CD36 signalling to enhance post-myocardial infarction cardiac dilation and mortality. Cardiovascular research 52 30169632
2021 CD8+ T cells inhibit metastasis and CXCL4 regulates its function. British journal of cancer 51 33795809
2018 Urinary angiostatin, CXCL4 and VCAM-1 as biomarkers of lupus nephritis. Arthritis research & therapy 51 29325582
2011 The Syk-kinase inhibitor R406 impairs platelet activation and monocyte tissue factor expression triggered by heparin-PF4 complex directed antibodies. Journal of thrombosis and haemostasis : JTH 48 21848694
2023 Chemokine CXCL4 interactions with extracellular matrix proteoglycans mediate widespread immune cell recruitment independent of chemokine receptors. Cell reports 47 36640356
2021 The C5a/C5a receptor 1 axis controls tissue neovascularization through CXCL4 release from platelets. Nature communications 47 34099640
2013 Platelet factor-4 (CXCL4/PF-4): an angiostatic chemokine for cancer therapy. Cancer letters 46 23337289
2018 Non-platelet-derived CXCL4 differentially regulates cytotoxic and regulatory T cells through CXCR3 to suppress the immune response to colon cancer. Cancer letters 45 30481563
2021 A prospective, blinded study of a PF4-dependent assay for HIT diagnosis. Blood 42 32898858
2020 Anti-CXCL4 Antibody Reactivity Is Present in Systemic Sclerosis (SSc) and Correlates with the SSc Type I Interferon Signature. International journal of molecular sciences 42 32707718
2022 Most anti-PF4 antibodies in vaccine-induced immune thrombotic thrombocytopenia are transient. Blood 41 35113987
2020 CXCL4 Links Inflammation and Fibrosis by Reprogramming Monocyte-Derived Dendritic Cells in vitro. Frontiers in immunology 40 33042127
2015 Platelet secretion of CXCL4 is Rac1-dependent and regulates neutrophil infiltration and tissue damage in septic lung damage. British journal of pharmacology 40 26478565
2011 Mechanism of platelet factor 4 (PF4) deficiency with RUNX1 haplodeficiency: RUNX1 is a transcriptional regulator of PF4. Journal of thrombosis and haemostasis : JTH 40 21129147
2009 The cathelicidin LL-37 activates human mast cells and is degraded by mast cell tryptase: counter-regulation by CXCL4. Journal of immunology (Baltimore, Md. : 1950) 40 19625657
2020 Prophage encoding toxin/antitoxin system PfiT/PfiA inhibits Pf4 production in Pseudomonas aeruginosa. Microbial biotechnology 39 32246813
2017 CXCL4 Exposure Potentiates TLR-Driven Polarization of Human Monocyte-Derived Dendritic Cells and Increases Stimulation of T Cells. Journal of immunology (Baltimore, Md. : 1950) 38 28515281
2008 The CXC-chemokine CXCL4 interacts with integrins implicated in angiogenesis. PloS one 38 18648521
2018 Surgical trauma contributes to progression of colon cancer by downregulating CXCL4 and recruiting MDSCs. Experimental cell research 37 30055136
2018 Polyreactive IgM initiates complement activation by PF4/heparin complexes through the classical pathway. Blood 37 30309891
2016 MKEY, a Peptide Inhibitor of CXCL4-CCL5 Heterodimer Formation, Protects Against Stroke in Mice. Journal of the American Heart Association 37 27633389
2014 Activation of p38-MAPK by CXCL4/CXCR3 axis contributes to p53-dependent intestinal apoptosis initiated by 5-fluorouracil. Cancer biology & therapy 37 24800927
2024 PF4 activates the c-Mpl-Jak2 pathway in platelets. Blood 36 37883794
2022 CXCL4 synergizes with TLR8 for TBK1-IRF5 activation, epigenomic remodeling and inflammatory response in human monocytes. Nature communications 36 35701499
2009 Heparin/PF4 antibodies formation after heparin treatment: temporal aspects and long-term follow-up. American heart journal 36 19249435
1999 Significantly elevated expression of PF4 (platelet factor 4) and eotaxin in the NOA mouse, a model for atopic dermatitis. Journal of human genetics 36 10319581
1975 Antigenic and antiheparin properties of human platelet factor 4 (PF4). Blood 36 803847
2020 CXCL4 triggers monocytes and macrophages to produce PDGF-BB, culminating in fibroblast activation: Implications for systemic sclerosis. Journal of autoimmunity 33 32284212
2017 The PF4/PPBP/CXCL5 Gene Cluster Is Associated with Periodontitis. Journal of dental research 33 28467728
2016 Platelet-derived CXCL4 regulates neutrophil infiltration and tissue damage in severe acute pancreatitis. Translational research : the journal of laboratory and clinical medicine 33 27183218
2016 Dual Roles for CXCL4 Chemokines and CXCR3 in Angiogenesis and Invasion of Pancreatic Cancer. Cancer research 32 27634764
2020 Structural Features and PF4 Functions that Occur in Heparin-Induced Thrombocytopenia (HIT) Complicated by COVID-19. Antibodies (Basel, Switzerland) 31 33050376
2019 Cleavage of anti-PF4/heparin IgG by a bacterial protease and potential benefit in heparin-induced thrombocytopenia. Blood 31 30917957
2015 Further insights into the anti-PF4/heparin IgM immune response. Thrombosis and haemostasis 31 26467272
2005 PF4/heparin complexes are T cell-dependent antigens. Blood 31 15845897
2024 ITGB6 modulates resistance to anti-CD276 therapy in head and neck cancer by promoting PF4+ macrophage infiltration. Nature communications 30 39152118
2016 CXCL4 and CXCL4L1 Differentially Affect Monocyte Survival and Dendritic Cell Differentiation and Phagocytosis. PloS one 30 27828999
2014 Environmental cues and genes involved in establishment of the superinfective Pf4 phage of Pseudomonas aeruginosa. Frontiers in microbiology 29 25520708
2023 Investigation of anti-PF4 versus anti-PF4/heparin reactivity using fluid-phase enzyme immunoassay for 4 anti-PF4 disorders: classic heparin-induced thrombocytopenia (HIT), autoimmune HIT, vaccine-induced immune thrombotic thrombocytopenia, and spontaneous HIT. Journal of thrombosis and haemostasis : JTH 28 37182698
2022 Natural history of PF4 antibodies in vaccine-induced immune thrombocytopenia and thrombosis. Blood 28 35263420
2012 Impaired CXCL4 expression in tumor-associated macrophages (TAMs) of ovarian cancers arising in endometriosis. Cancer biology & therapy 28 22555803
2015 Critical role of CD4 T cells in PF4/heparin antibody production in mice. Blood 26 25595736
2022 Urine ALCAM, PF4 and VCAM-1 Surpass Conventional Metrics in Identifying Nephritis Disease Activity in Childhood-Onset Systemic Lupus Erythematosus. Frontiers in immunology 25 35720325
2015 CXCL4 mediates tumor regrowth after chemotherapy by suppression of antitumor immunity. Cancer biology & therapy 25 26479470
2014 Angiostatic, tumor inflammatory and anti-tumor effects of CXCL4(47-70) and CXCL4L1(47-70) in an EGF-dependent breast cancer model. Oncotarget 25 25373734
2010 CXC chemokine ligand 4 (CXCL4) down-regulates CC chemokine receptor expression on human monocytes. Innate immunity 25 21088050
2018 Anti-PF4/heparin antibodies are increased in hospitalized patients with bacterial sepsis. Thrombosis research 23 30273811
2009 Platelet factor 4 (CXCL4) facilitates human macrophage infection with HIV-1 and potentiates virus replication. Innate immunity 23 19773294
2022 Pf4 Phage Variant Infection Reduces Virulence-Associated Traits in Pseudomonas aeruginosa. Microbiology spectrum 22 36036571
2019 CXCL12-CXCL4 heterodimerization prevents CXCL12-driven breast cancer cell migration. Cellular signalling 22 31785332
2014 CXCL4L1 and CXCL4 signaling in human lymphatic and microvascular endothelial cells and activated lymphocytes: involvement of mitogen-activated protein (MAP) kinases, Src and p70S6 kinase. Angiogenesis 22 24469069
2024 Hyperactivation of β-catenin signal in hepatocellular carcinoma recruits myeloid-derived suppressor cells through PF4-CXCR3 axis. Cancer letters 21 38307410
2022 Hypoxia and TLR9 activation drive CXCL4 production in systemic sclerosis plasmacytoid dendritic cells via mtROS and HIF-2α. Rheumatology (Oxford, England) 21 34559222
2022 Quantitative interpretation of PF4/heparin-EIA optical densities in predicting platelet-activating VITT antibodies. Journal of thrombosis and haemostasis : JTH 21 36006172
2004 Upstream stimulatory factors stimulate transcription through E-box motifs in the PF4 gene in megakaryocytes. Blood 20 15187018
2022 Filamentous Pseudomonas Phage Pf4 in the Context of Therapy-Inducibility, Infectivity, Lysogenic Conversion, and Potential Application. Viruses 19 35746731
2022 CXCL4-RNA Complexes Circulate in Systemic Sclerosis and Amplify Inflammatory/Pro-Fibrotic Responses by Myeloid Dendritic Cells. International journal of molecular sciences 19 36614095
2018 Fibronectin modulates formation of PF4/heparin complexes and is a potential factor for reducing risk of developing HIT. Blood 19 30573633
2022 The c-di-GMP Phosphodiesterase PipA (PA0285) Regulates Autoaggregation and Pf4 Bacteriophage Production in Pseudomonas aeruginosa PAO1. Applied and environmental microbiology 18 35638845
2010 CXCL4-induced monocyte survival, cytokine expression, and oxygen radical formation is regulated by sphingosine kinase 1. European journal of immunology 18 20104488
2023 New perspectives on the induction and acceleration of immune-associated thrombosis by PF4 and VWF. Frontiers in immunology 17 36926331
2022 Differential Effects of Platelet Factor 4 (CXCL4) and Its Non-Allelic Variant (CXCL4L1) on Cultured Human Vascular Smooth Muscle Cells. International journal of molecular sciences 17 35054772
2022 High levels of PF4, VEGF-A, and classical monocytes correlate with the platelets count and inflammation during active tuberculosis. Frontiers in immunology 17 36325331
2016 Regulatory role of Megakaryocytes on Hematopoietic Stem Cells Quiescence by CXCL4/PF4 in Bone Marrow Niche. Leukemia research 17 26803701

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