Affinage

SFTPD

Pulmonary surfactant-associated protein D · UniProt P35247

Length
375 aa
Mass
37.7 kDa
Annotated
2026-04-28
100 papers in source corpus 34 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SP-D (SFTPD) is a collagen-containing C-type lectin collectin that assembles as disulfide-stabilized trimers, dodecamers, and higher-order multimers to regulate pulmonary surfactant phospholipid homeostasis and innate immune defense in the lung. The N-terminal and collagen domains govern oligomerization and are required for macrophage regulation and surfactant lipid homeostasis, while the homotrimeric carbohydrate recognition domain (CRD) mediates calcium-dependent binding to glucosylceramide, phosphatidylinositol, bacterial membrane lipids, and viral hemagglutinin—enabling pathogen aggregation, neutrophil and monocyte chemoattraction, NETosis suppression, and engagement of SIRPα/SIRPβ receptors (PMID:8006040, PMID:8040272, PMID:10956621, PMID:11278637, PMID:16636058, PMID:22511785, PMID:31872075). Transcription of SFTPD is co-activated by NFATc3 in complex with TTF-1, and post-translational S-nitrosylation disrupts oligomerization and abrogates immune-regulatory functions including inhibition of eosinophil extracellular DNA trap formation (PMID:15173172, PMID:29733456). SP-D deficiency in mice causes surfactant lipid accumulation, foamy macrophage infiltration, progressive emphysema, and dysregulated pulmonary T cell activation, with surfactant homeostasis correctable by lung-specific SP-D re-expression but emphysema being irreversible once established (PMID:10956621, PMID:12091242, PMID:12163500).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1989 High

    Identification of SP-D as a distinct collagenous surfactant glycoprotein that forms disulfide-bonded trimers of 43 kDa subunits resolved the question of whether alveolar lining fluid contained collectins beyond SP-A.

    Evidence Biochemical purification, 2D-PAGE, gel filtration, and peptide sequencing from rat type II cells

    PMID:2675969

    Open questions at the time
    • Full quaternary structure not yet determined
    • Human homolog not yet cloned
    • Functional role unknown
  2. 1991 High

    Cloning of human SP-D cDNA established it as a C-type lectin with a conserved CRD containing calcium-dependent saccharide binding, placing it in the mannose-binding lectin family and predicting innate immune functions.

    Evidence cDNA library screening, DNA sequencing, immunoprecipitation of translation products, peptide antibody validation

    PMID:1898081

    Open questions at the time
    • Ligand specificity of the CRD undefined
    • Structural basis of carbohydrate recognition unknown
  3. 1992 High

    Identification of glucosylceramide and phosphatidylinositol as specific SP-D ligands, together with ultrastructural localization showing distinct intracellular trafficking from SP-A, established that SP-D has unique lipid-binding specificity and a secretory pathway separate from lamellar body-associated surfactant components.

    Evidence TLC overlay, mass spectrometry, liposome reconstitution binding, immunogold EM with double-labeling in rat lung

    PMID:1457414 PMID:1527377 PMID:1530650

    Open questions at the time
    • Physiological consequence of lipid binding unclear
    • No information on pathogen binding
  4. 1994 High

    Electron microscopy and hydrodynamic analysis revealed SP-D assembles as a cruciform dodecamer of four trimeric arms, each 46 nm long, explaining how multivalent CRD presentation enables high-avidity pathogen recognition including influenza A virus aggregation and enhanced neutrophil function.

    Evidence Freeze-dried EM, pepsin/collagenase digestion, hemagglutination inhibition, neutrophil binding and respiratory burst assays

    PMID:8006040 PMID:8040272

    Open questions at the time
    • Atomic-resolution structure unavailable
    • Mechanism of neutrophil protection not defined at receptor level
  5. 1996 High

    Demonstration that higher-order multimers of dodecamers are several-fold more potent than dodecamers at viral aggregation and neutrophil protection established a valency-dependent model for SP-D innate immune function.

    Evidence Recombinant hSP-D in CHO cells fractionated by gel filtration; EM, hemagglutination inhibition, neutrophil protection assays

    PMID:8944718

    Open questions at the time
    • Determinants of multimerization beyond dodecamer undefined
    • In vivo relevance of multimer vs. dodecamer not tested
  6. 2000 High

    SP-D knockout and transgenic rescue experiments demonstrated that SP-D locally regulates surfactant phospholipid pool size—loss causes 3–4-fold lipid accumulation and accelerated large-to-small aggregate conversion, both corrected by lung-specific SP-D re-expression—establishing SP-D as a non-redundant regulator of surfactant homeostasis.

    Evidence SP-D gene-targeted mice, SP-C promoter transgenic rescue, BAL phospholipid measurements, radiolabeled kinetics

    PMID:10666121 PMID:10956621

    Open questions at the time
    • Molecular mechanism of lipid homeostasis regulation unclear
    • Whether SP-D acts on type II cells vs. macrophages not resolved
  7. 2001 High

    Dodecameric assembly via N-terminal Cys15/20 disulfide bonds was shown to be required for surfactant homeostasis and prevention of emphysema but dispensable for antiviral activity, dissecting oligomerization-dependent and -independent functions; epistasis with GM-CSF knockout revealed independent pathways for macrophage activation and lipid catabolism.

    Evidence Cys15/20Ser mutant transgene in SP-D null mice; SP-D/GM-CSF double knockout with BAL lipid, morphological, and stereological analysis

    PMID:11278637 PMID:11350793 PMID:11504698

    Open questions at the time
    • Direct receptor or signaling target on macrophages for N-terminal/collagen domain not identified
    • Mechanism of emphysema development unresolved
  8. 2002 High

    Domain-swap chimeras and conditional induction/withdrawal experiments separated SP-D functions into collagen/N-terminal-dependent (macrophage regulation, emphysema prevention) and CRD-dependent (pathogen clearance, lipid regulation) modules, and showed emphysema is irreversible once established while surfactant homeostasis is rapidly correctable.

    Evidence SP-D/conglutinin chimeric transgene, doxycycline-regulated conditional transgene in SP-D null mice, CRD mutagenesis with Mycoplasma binding

    PMID:11916969 PMID:11956209 PMID:12163500

    Open questions at the time
    • Specific signaling pathways downstream of collagen domain engagement unknown
    • Whether emphysema reflects a developmental window or ongoing tissue destruction not fully resolved
  9. 2002 High

    SP-D null mice display persistent pulmonary T cell activation with elevated CD4+/CD8+ activation markers and proinflammatory cytokines, establishing SP-D as a local immunoregulatory factor that suppresses adaptive immune activation in the lung.

    Evidence Flow cytometry of intrapulmonary lymphocytes from SP-D−/− mice, cytokine ELISA, RT-PCR

    PMID:12091242

    Open questions at the time
    • Whether T cell suppression is direct or mediated via macrophage/dendritic cell regulation unknown
    • Human relevance not tested
  10. 2004 High

    Identification of NFATc3 as a transcriptional co-activator of Sftpd, synergizing with TTF-1, revealed a calcineurin-dependent regulatory pathway for SP-D expression in lung epithelium.

    Evidence Promoter-reporter assays, gel shift, DNase I footprinting, calcineurin/cyclosporin inhibition, co-immunoprecipitation

    PMID:15173172

    Open questions at the time
    • Upstream signals activating calcineurin/NFATc3 in type II cells not identified
    • Relevance of this pathway to disease-associated SP-D deficiency unknown
  11. 2005 High

    The common Met11Thr polymorphism was shown to alter SP-D oligomerization: Thr11 lacks the highest-order multimers and preferentially binds isolated LPS over intact organisms, providing a structural basis for genetic variation in innate immune function.

    Evidence Genotyping, gel filtration, AFM of purified protein, ELISA, mannan/virus binding assays

    PMID:15661913

    Open questions at the time
    • Clinical outcomes associated with Met11Thr not mechanistically dissected
    • Whether Thr11 affects surfactant homeostasis not tested
  12. 2006 High

    Crystallographic and mutagenesis studies identified Phe335 as a critical CRD residue that stacks with terminal sugar rings to determine ligand specificity, while in vivo collagen-domain deletion confirmed that the collagen region is required for macrophage regulation and surfactant homeostasis but dispensable for innate immune pathogen clearance.

    Evidence Crystal structure of neck+CRD with ligands, Phe335 site-directed mutagenesis, collagen-deletion transgene in SP-D null mice

    PMID:16500946 PMID:16636058 PMID:16787926

    Open questions at the time
    • Full-length dodecameric structure not solved
    • Whether Phe335 variants exist in human populations unknown
  13. 2009 High

    SP-D was found to bind SIRPα and SIRPβ via their D3 immunoglobulin domains in a calcium- and glycan-dependent manner at a site distinct from CD47, identifying a receptor pathway for SP-D signaling on myeloid cells.

    Evidence Domain-deleted SIRPα/SIRPβ binding assays, N-glycosylation site mutagenesis, binding to neutrophil surface SIRPα

    PMID:22511785

    Open questions at the time
    • Downstream signaling consequences of SP-D–SIRPα interaction not characterized
    • Whether SIRPα mediates SP-D's anti-inflammatory functions in vivo not tested
  14. 2018 High

    S-nitrosylation of SP-D was identified as a post-translational modification that disrupts oligomerization and abolishes eosinophil DNA trap inhibition, linking oxidative/nitrosative stress to loss of SP-D immune-regulatory function in conditions like asthma; AFM quantification established dodecamers as the predominant assembly form stabilized by N-terminal non-covalent interactions.

    Evidence AFM of recombinant and patient-derived SP-D, in vitro S-nitrosylation, eosinophil trap assays, Sftpd−/− mice with allergen/ozone challenge

    PMID:29626540 PMID:29733456

    Open questions at the time
    • Identity of S-nitrosylated cysteine residues not mapped
    • Whether S-nitrosylation occurs in vivo at sufficient stoichiometry to regulate function not quantified
  15. 2019 High

    SP-D was shown to attenuate LPS-induced NETosis and to rescue surfactant biophysical function from NET-mediated inhibition, establishing a protective feedback loop wherein SP-D prevents NET-induced surfactant dysfunction during inflammation.

    Evidence Human neutrophil NETosis assay, Sftpd−/− mouse LPS model, surface activity measurements of surfactant with/without NETs and SP-D

    PMID:31872075

    Open questions at the time
    • Receptor on neutrophils mediating SP-D NETosis suppression not identified
    • Whether NET inhibition operates through SIRPα or another pathway unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the signaling pathways downstream of SP-D–SIRPα engagement on macrophages and neutrophils, the molecular mechanism by which SP-D regulates surfactant lipid pool size (direct type II cell vs. macrophage-mediated), the full-length dodecameric atomic structure, and whether S-nitrosylation site identity and stoichiometry explain disease-associated SP-D dysfunction.
  • No atomic structure of full-length SP-D dodecamer
  • Signaling downstream of SIRPα/β engagement uncharacterized
  • Direct vs. macrophage-mediated regulation of surfactant homeostasis unresolved
  • In vivo relevance of S-nitrosylation stoichiometry not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0048018 receptor ligand activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 4 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-382551 Transport of small molecules 4
Partners
MMP9NFATC3NKX2-1SIRPASIRPBSPA

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 SP-D (CP4) was identified as a distinct collagenous glycoprotein synthesized by rat type II pulmonary epithelial cells, forming high apparent molecular mass complexes of disulfide-bonded trimers of 43-kDa subunits, and was formally designated 'surfactant protein D'. Biochemical purification (BaSO4 adsorption, reverse-phase HPLC), amino acid analysis, 2D-IEF/SDS-PAGE, gel filtration, CNBr peptide sequencing Biochemistry High 2675969
1991 Human SP-D contains a C-type lectin carbohydrate recognition domain (CRD) with calcium-dependent saccharide binding, confirmed by cDNA sequencing, immunoprecipitation of translation products, and peptide antibody reactivity; the CRD contains conserved cysteine residues and shows high homology with mannose-binding subfamily C-type lectins. cDNA library screening, DNA sequencing, immunoprecipitation, synthetic peptide antibodies, amino-terminal microsequencing Archives of biochemistry and biophysics High 1898081
1991 Native SP-D counteracts the inhibitory effect of SP-A on phospholipid secretion by alveolar type II cells by competing with SP-A for high-affinity binding to type II cells; this activity requires SP-D-associated lipids and involves direct SP-D–SP-A interaction. Primary type II cell secretion assay, radiolabeled SP-A competition binding, nitrocellulose overlay, butanol extraction of SP-D The Biochemical journal Medium 1930130
1991 SP-D mRNA and protein first appear in rat lung at gestational day 21 in cuboidal epithelial cells lining immature airspaces, and in adult lung in type II and nonciliated bronchiolar cells, with SP-D secreted into amniotic fluid, establishing developmental expression pattern. Northern hybridization, immunoperoxidase staining, cell-free translation, affinity chromatography American journal of respiratory cell and molecular biology Medium 1878250
1992 SP-D localizes in type II cells (endoplasmic reticulum, Golgi, multivesicular bodies but not lamellar bodies), Clara cells (secretory granules at apical domain), and alveolar macrophages (endocytotic structures); in Clara cells SP-D co-localizes with SP-A in the same granules but is confined to the periphery while SP-A distributes throughout. Immunogold electron microscopy, double-labeling with anti-SP-A and lysosomal markers, BSAG endocytotic pathway tracing Journal of histochemistry and cytochemistry High 1527377
1992 SP-D binds exclusively to glucosylceramide (GlcCer) among glycolipids tested, in a calcium-dependent and antibody-inhibitable manner; Mg2+ cannot substitute for Ca2+. TLC overlay with 125I-labeled SP-D, competition assay, antibody inhibition Biochemical and biophysical research communications Medium 1530650
1992 SP-D binds phosphatidylinositol (PI) as its major glycolipid ligand in surfactant in a calcium-dependent, saccharide-inhibitable manner, including binding to PI in lipid bilayer liposomes. 2D-TLC overlay with 125I-SP-D, affinity purification, mass spectrometry, Percoll density gradient liposome binding Biochemistry High 1457414
1993 SP-D is encoded on chromosome 10q22.2-23.1; the collagen domain is encoded on five exons including four tandem 117-bp exons, while the signal peptide/N-terminal domain, CRD, and linking sequence are each on a single exon, consistent with modular evolution. Genomic clone characterization, sequencing, segregation analysis with HindIII, fluorescence in situ hybridization, PCR with somatic cell hybrids The Journal of biological chemistry High 8428971
1994 SP-D forms a dodecameric quaternary structure assembled as homopolymers of four identical trimeric subunits, each arm 46 nm long with a globular CRD terminal expansion; interchain disulfide bonds at the N-terminal domain stabilize trimer interactions, and higher-order multimeric assemblies also occur. Electron microscopy (freeze-dried), hydrodynamic analysis, pepsin digestion, sulfhydryl reduction, bacterial collagenase digestion The Journal of biological chemistry High 8006040
1994 SP-D potently inhibits influenza A virus (IAV) hemagglutination and causes viral aggregation via its calcium-dependent carbohydrate-binding CRD; SP-D enhances neutrophil binding of IAV and respiratory burst, and diminishes neutrophil dysfunction caused by IAV. Hemagglutination inhibition assay, viral aggregation assay, neutrophil binding assay, respiratory burst measurement, calcium/saccharide inhibition controls The Journal of clinical investigation High 8040272
1995 SP-D acts as a chemoattractant for human neutrophils and monocytes in a dose-dependent, saccharide-inhibitable (maltose-sensitive) manner via interactions involving the carboxy-terminal lectin domain. Modified Boyden chamber chemotaxis assay, checkerboard analysis, antibody and sugar inhibition American journal of respiratory cell and molecular biology Medium 7695920
1996 Higher-order multimers of human SP-D (multimers of dodecamers) are several-fold more potent than dodecamers at causing IAV aggregation and protecting neutrophils from IAV deactivation, demonstrating valency-dependent CRD interactions; the propensity to form multimers is determined by primary structure. Recombinant hSP-D expression in CHO cells, gel filtration, electron microscopy, hemagglutination inhibition, neutrophil protection assay The American journal of physiology High 8944718
1999 The trimeric carbohydrate recognition domain (CRD) of SP-D is sufficient for chemotactic activity toward neutrophils, with peak activity at 10^-10 M; activity is abolished by 20 mM maltose, indicating CRD-dependent recognition. Recombinant neck+CRD expression in E. coli, gel-filtration characterization, Boyden chamber chemotaxis, maltose inhibition The American journal of physiology Medium 9887065
2000 SP-D deficiency causes a 3-4 fold increase in alveolar surfactant lipids associated with accelerated conversion of large- to small-aggregate surfactant; pulmonary-specific transgenic re-expression of SP-D corrects the lipid accumulation, demonstrating that SP-D acts locally to regulate surfactant phospholipid homeostasis. SP-D gene-targeted mice, SP-C promoter-driven transgene, bronchoalveolar lavage phospholipid measurements, radiolabeled phospholipid kinetics American journal of physiology. Lung cellular and molecular physiology High 10666121 10956621
2001 Dodecameric (disulfide cross-linked oligomeric) assembly of SP-D is required for regulation of surfactant phospholipid homeostasis and prevention of emphysema and foamy macrophages in vivo; trimeric SP-D (Cys15/20 → Ser mutant) fails to rescue these phenotypes but does not affect antiviral activity. Transgenic mice expressing Cys15/20Ser mutant rSP-D in SP-D null background, bronchoalveolar lavage lipid and morphological analysis The Journal of biological chemistry High 11278637
2001 SP-D and GM-CSF regulate surfactant homeostasis by distinct mechanisms: double-knockout mice show approximately additive phospholipid accumulation, and GM-CSF expression corrects GM-CSF-dependent catabolism defects but not SP-D-null lung pathology. SP-D/GM-CSF double knockout mice, GM-CSF lung-selective transgene rescue, saturated phosphatidylcholine pool size measurements American journal of physiology. Lung cellular and molecular physiology High 11504698
2001 GM-CSF mediates alveolar macrophage proliferation and type II cell hypertrophy in SP-D null mice; double null SP-D/GM-CSF mice show large but not foamy macrophages and mostly normal type II cells, while emphysema persists, separating GM-CSF-dependent from GM-CSF-independent SP-D functions. SP-D/GM-CSF double knockout breeding, BAL analysis, electron and light microscopy American journal of physiology. Lung cellular and molecular physiology High 11350793
2002 Human SP-D binds Mycoplasma pneumoniae via calcium-dependent, carbohydrate-recognition-domain-mediated interactions with bacterial membrane lipids (not proteins); a CRD tandem mutant (E321Q/N323D) abolishes binding, directly implicating the CRD. Ca2+/EGTA-dependent binding assays, protease pre-treatment of membranes, 2D-TLC overlay, CRD mutagenesis The Journal of biological chemistry High 11916969
2002 Restoring SP-D expression in adult SP-D null mice via doxycycline-regulated transgene corrects surfactant lipid abnormalities and alveolar macrophage phenotype within days, but established emphysema is not reversed; loss of SP-D in corrected adults causes focal emphysema but not phospholipid abnormalities, showing these pathways are separable. Conditional doxycycline-regulated transgene in SP-D null mice, BAL lipid assays, morphometric analysis The Journal of biological chemistry High 12163500
2002 SP-D/conglutinin chimera (SP-D N-terminal/collagen + conglutinin neck+CRD) corrects surfactant phospholipid abnormalities and viral clearance defects in SP-D null mice but does not correct ongoing lung inflammation and emphysema, indicating distinct roles for CRD identity versus N-terminal domains in different SP-D functions. Chimeric transgene expression in SP-D null mice, BAL lipid assay, influenza A clearance assay, lung morphology The Journal of biological chemistry High 11956209
2002 SP-D null mice develop persistent pulmonary T cell activation (increased CD4+ and CD8+ T cells expressing CD69 and CD25, elevated BAL CD4 lymphocytes, increased IL-12 and IL-6), demonstrating a local immunoregulatory role for SP-D in suppressing T cell responses in vivo. Flow cytometry of intrapulmonary lymphocytes from SP-D-/- mice, RNase protection assay, RT-PCR, ELISA for cytokines American journal of respiratory cell and molecular biology High 12091242
2004 NFATc3 regulates SP-D gene (Sftpd) transcription via an NFAT-dependent enhancer in the Sftpd promoter; NFATc3 and TTF-1 synergize, co-immunoprecipitate, and physically interact in vitro to activate Sftpd transcription in lung epithelial cells. Promoter-reporter assays, gel supershift/DNase I footprinting, calcineurin/cyclosporin/VIVIT inhibition, co-immunoprecipitation, in vitro protein interaction The Journal of biological chemistry High 15173172
2004 GM-CSF is required for type II cell hyperplasia and hypertrophy in SP-D-deficient mice but not for emphysema development; emphysema-like changes in SP-D null mice are independent of GM-CSF-dependent macrophage activity. SP-D/GM-CSF double knockout mice, design-based stereology at light and electron microscope levels American journal of physiology. Lung cellular and molecular physiology High 15310555
2005 A common SFTPD polymorphism at codon 11 (Met11Thr) influences SP-D oligomerization: Thr11 SP-D lacks the highest molecular weight multimeric form, has lower serum levels, and shows preferential binding to isolated LPS rather than intact bacteria/viruses, whereas Met11 multimers preferentially bind intact organisms. Genotyping, gel filtration, atomic force microscopy of purified protein, ELISA, mannan- and virus-binding assays Journal of immunology High 15661913
2006 The collagenous domain of SP-D is required for regulation of pulmonary macrophage activation, airspace remodeling, and surfactant lipid homeostasis in vivo, but is dispensable for assembly of disulfide-stabilized oligomers and for innate immune response to influenza A. Collagen deletion mutant SP-D transgene in wild-type and Sftpd-/- mice, BAL lipid assay, influenza A clearance, lung morphology, surfactant ultrastructure The Journal of biological chemistry High 16787926
2006 Phenylalanine 335 in the SP-D CRD mediates preferential binding to aromatic glycosides and maltotriose via ring-stacking interactions; Phe335Leu substitution reduces affinity for maltotriose and p-nitrophenyl-maltoside, and Phe335Ala abolishes mannan binding; crystallographic analysis shows stacking of the terminal glucose or nitrophenyl ring with the Phe335 aromatic ring. Site-directed mutagenesis, fluorescence polarization binding assay, crystallographic analysis of neck+CRD with ligands The Journal of biological chemistry High 16636058
2006 Neither full-length SP-A nor chimeric NH2-SP-A/SP-D (SP-A N-terminal+collagen fused to SP-D neck+CRD) can substitute for SP-D in correcting emphysema, foamy macrophages, or lipid accumulation in SP-D null mice; SP-D N-terminal and collagen domains are required for proper oligomerization and surfactant lipid association. Transgenic expression of chimeric proteins in Sftpd-/- mice, BAL lipid/protein assays, lung morphology American journal of physiology. Lung cellular and molecular physiology High 16500946
2009 SP-D binds to the membrane-proximal immunoglobulin-like domain (D3) of SIRPα in a calcium- and carbohydrate-dependent manner via specific N-glycosylated residues on D3; SP-D also binds the analogous D3 domain of SIRPβ; the SP-D binding site on SIRPα is distinct from the CD47 binding site on D1. Domain-deleted SIRPα/SIRPβ mutant binding assays, N-glycosylation site mutagenesis, binding to SIRPα on human neutrophils and differentiated neutrophil-like cells The Journal of biological chemistry High 22511785
2012 MMP-9 cleaves SP-D in vitro, abolishing its ability to aggregate bacteria and enhance phagocytosis by alveolar macrophages, while preserving LPS binding; MMP-9 cleaves SP-D more efficiently than neutrophil elastase at physiological calcium concentrations. In vitro protease cleavage assay, bacterial aggregation assay, macrophage phagocytosis assay, solid-phase LPS binding PloS one Medium 22860023
2018 SP-D directly binds to eosinophil membranes in a concentration- and carbohydrate-dependent manner and inhibits eosinophil extracellular DNA trap formation; S-nitrosylation of SP-D (mimicking iNOS/oxidative conditions in asthma) causes de-oligomerization of SP-D and abolishes its ability to inhibit DNA trap formation. Confocal imaging with recombinant SP-D, murine and human eosinophil assays, iNOS inhibition, S-nitrosylation in vitro, Sftpd-/- mice with allergen/ozone challenge Journal of leukocyte biology High 29733456
2018 Dodecamers are the predominant SP-D oligomeric form (>50% by mass); dodecamer formation requires two hexamers as a minimal unit and is stabilized by non-covalent, ionic, and hydrophobic interactions between N-terminal domains and proximal collagen stems; acidic conditions promote compact dodecamer configuration. Atomic force microscopy (AFM) of recombinant and patient-derived hSP-D, electrophoresis, comparative analysis at different pH Journal of molecular biology High 29626540
2019 SP-D attenuates LPS-mediated NETosis in human neutrophils by binding LPS; SP-D deficiency in mice leads to excess NET formation in lungs during LPS-mediated inflammation; NETs inhibit pulmonary surfactant biophysical function in the absence of SP-D, and SP-D reverses NET-mediated surfactant inhibition. Human neutrophil NETosis assay with recombinant SP-D, Sftpd-/- mouse LPS model, surfactant biophysical assay (surface activity measurement) Communications biology High 31872075
1998 KGF increases SP-D mRNA and protein secretion in rat alveolar type II cells in primary culture at the air-liquid interface; TPA+terbutaline stimulates phosphatidylcholine and SP-A secretion but not SP-D, indicating SP-D secretion is regulated by a distinct pathway from SP-A. Primary rat type II cell culture, Northern blot, ELISA for SP-D protein in apical medium, [3H]PC secretion assay American journal of respiratory cell and molecular biology Medium 9476903

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Surfactant proteins SP-A and SP-D: structure, function and receptors. Molecular immunology 410 16213021
1994 Evidence for a protective role of pulmonary surfactant protein D (SP-D) against influenza A viruses. The Journal of clinical investigation 267 8040272
1994 Molecular structure of pulmonary surfactant protein D (SP-D). The Journal of biological chemistry 186 8006040
1989 Purification and biochemical characterization of CP4 (SP-D), a collagenous surfactant-associated protein. Biochemistry 175 2675969
1992 Immunocytochemical localization of surfactant protein D (SP-D) in type II cells, Clara cells, and alveolar macrophages of rat lung. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 166 1527377
2005 The lung collectins, SP-A and SP-D, modulate pulmonary innate immunity. Molecular immunology 154 15589315
2000 Polymorphisms of human SP-A, SP-B, and SP-D genes: association of SP-B Thr131Ile with ARDS. Clinical genetics 154 11076040
2012 An Insight into the Diverse Roles of Surfactant Proteins, SP-A and SP-D in Innate and Adaptive Immunity. Frontiers in immunology 148 22701116
1999 Novel, non-radioactive, simple and multiplex PCR-cRFLP methods for genotyping human SP-A and SP-D marker alleles. Disease markers 141 10689550
1996 Interactions of recombinant human pulmonary surfactant protein D and SP-D multimers with influenza A. The American journal of physiology 129 8944718
2005 A common polymorphism in the SFTPD gene influences assembly, function, and concentration of surfactant protein D. Journal of immunology (Baltimore, Md. : 1950) 123 15661913
1998 Structure, biologic properties, and expression of surfactant protein D (SP-D). Biochimica et biophysica acta 122 9813367
2021 SP-A and SP-D: Dual Functioning Immune Molecules With Antiviral and Immunomodulatory Properties. Frontiers in immunology 113 33542724
2002 Immunolocalization of surfactant protein-D (SP-D) in human fetal, newborn, and adult tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 111 11967276
1998 Organization of the human SP-A and SP-D loci at 10q22-q23. Physical and radiation hybrid mapping reveal gene order and orientation. American journal of respiratory cell and molecular biology 105 9490653
2016 Comparative Study of Circulating MMP-7, CCL18, KL-6, SP-A, and SP-D as Disease Markers of Idiopathic Pulmonary Fibrosis. Disease markers 103 27293304
1993 Genomic organization of human surfactant protein D (SP-D). SP-D is encoded on chromosome 10q22.2-23.1. The Journal of biological chemistry 99 8428971
2003 Surfactant protein D (SP-D) serum levels in patients with community-acquired pneumonia. Clinical immunology (Orlando, Fla.) 97 12865068
1994 Surfactant proteins A (SP-A) and D (SP-D): levels in human amniotic fluid and localization in the fetal membranes. Biochimica et biophysica acta 96 8305484
2005 Susceptibility of mice genetically deficient in the surfactant protein (SP)-A or SP-D gene to pulmonary hypersensitivity induced by antigens and allergens of Aspergillus fumigatus. Journal of immunology (Baltimore, Md. : 1950) 90 15905537
1995 Interactions of pulmonary surfactant protein D (SP-D) with human blood leukocytes. American journal of respiratory cell and molecular biology 89 7695920
2000 Surfactant metabolism in SP-D gene-targeted mice. American journal of physiology. Lung cellular and molecular physiology 87 10956621
2010 Prescreening based on the presence of CT-scan abnormalities and biomarkers (KL-6 and SP-D) may reduce severe radiation pneumonitis after stereotactic radiotherapy. Radiation oncology (London, England) 86 20459699
1993 Purification and characterization of a bovine serum lectin (CL-43) with structural homology to conglutinin and SP-D and carbohydrate specificity similar to mannan-binding protein. The Journal of biological chemistry 84 8486682
1991 Human surfactant protein D: SP-D contains a C-type lectin carbohydrate recognition domain. Archives of biochemistry and biophysics 83 1898081
2004 Effects of ageing and smoking on SP-A and SP-D levels in bronchoalveolar lavage fluid. The European respiratory journal 81 15572540
1998 KGF increases SP-A and SP-D mRNA levels and secretion in cultured rat alveolar type II cells. American journal of respiratory cell and molecular biology 81 9476903
1991 Developmental expression of pulmonary surfactant protein D (SP-D). American journal of respiratory cell and molecular biology 71 1878250
2007 Truncated recombinant human SP-D attenuates emphysema and type II cell changes in SP-D deficient mice. Respiratory research 70 17915009
1992 The major glycolipid recognized by SP-D in surfactant is phosphatidylinositol. Biochemistry 70 1457414
2012 Mice deficient in surfactant protein A (SP-A) and SP-D or in TLR2 manifest delayed parturition and decreased expression of inflammatory and contractile genes. Endocrinology 69 23183169
2000 Pulmonary-specific expression of SP-D corrects pulmonary lipid accumulation in SP-D gene-targeted mice. American journal of physiology. Lung cellular and molecular physiology 69 10666121
2015 The usefulness of KL-6 and SP-D for the diagnosis and management of chronic hypersensitivity pneumonitis. Respiratory medicine 64 26481343
2005 Surfactant proteins SP-A and SP-D in human health and disease. Archivum immunologiae et therapiae experimentalis 60 16314824
2010 Role of surfactant protein A and D (SP-A and SP-D) in human antiviral host defense. Frontiers in bioscience (Scholar edition) 59 20036966
2008 Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study. Respiratory research 58 18226251
2003 Attenuated allergic airway hyperresponsiveness in C57BL/6 mice is associated with enhanced surfactant protein (SP)-D production following allergic sensitization. Respiratory research 57 14748931
2001 Activity of pulmonary surfactant protein-D (SP-D) in vivo is dependent on oligomeric structure. The Journal of biological chemistry 57 11278637
1993 Assignment of the human pulmonary surfactant protein D gene (SFTP4) to 10q22-q23 close to the surfactant protein A gene cluster. Genomics 55 8406480
2010 Susceptibility of mice genetically deficient in SP-A or SP-D gene to invasive pulmonary aspergillosis. Molecular immunology 52 20413160
2004 GM-CSF mediates alveolar epithelial type II cell changes, but not emphysema-like pathology, in SP-D-deficient mice. American journal of physiology. Lung cellular and molecular physiology 51 15310555
2016 Surfactant proteins, SP-A and SP-D, in respiratory fungal infections: their role in the inflammatory response. Respiratory research 48 27250970
2005 Polymorphisms in the human surfactant protein-D (SFTPD) gene: strong evidence that serum levels of surfactant protein-D (SP-D) are genetically influenced. Immunogenetics 48 15700120
2012 Surfactant protein D (SP-D) alters cellular uptake of particles and nanoparticles. Nanotoxicology 47 22551051
2002 Lymphocyte activation in the lungs of SP-D null mice. American journal of respiratory cell and molecular biology 46 12091242
2006 Correction of pulmonary abnormalities in Sftpd-/- mice requires the collagenous domain of surfactant protein D. The Journal of biological chemistry 45 16787926
1991 Ontogeny of surfactant apoprotein D, SP-D, in the rat lung. Biochimica et biophysica acta 45 2049389
2019 SP-D attenuates LPS-induced formation of human neutrophil extracellular traps (NETs), protecting pulmonary surfactant inactivation by NETs. Communications biology 44 31872075
2004 Nuclear factor of activated T cells regulates transcription of the surfactant protein D gene (Sftpd) via direct interaction with thyroid transcription factor-1 in lung epithelial cells. The Journal of biological chemistry 44 15173172
2002 Complementation of pulmonary abnormalities in SP-D(-/-) mice with an SP-D/conglutinin fusion protein. The Journal of biological chemistry 44 11956209
2002 Clinical significance of serum surfactant protein D (SP-D) in patients with polymyositis/dermatomyositis: correlation with interstitial lung disease. Rheumatology (Oxford, England) 44 12421999
2001 Localization and functions of SP-A and SP-D at mucosal surfaces. Pediatric pathology & molecular medicine 44 11486736
1992 Binding specificity of lung surfactant protein SP-D for glucosylceramide. Biochemical and biophysical research communications 43 1530650
2001 Pneumocystis carinii pneumonia alters expression and distribution of lung collectins SP-A and SP-D. The Journal of laboratory and clinical medicine 42 11385364
2002 Serum SP-D is a marker of lung injury in rats. American journal of physiology. Lung cellular and molecular physiology 41 11880309
2018 Genetic Association of Pulmonary Surfactant Protein Genes, SFTPA1, SFTPA2, SFTPB, SFTPC, and SFTPD With Cystic Fibrosis. Frontiers in immunology 40 30333828
2002 Surfactant proteins SP-A and SP-D as modulators of the allergic inflammation in asthma. Pathobiology : journal of immunopathology, molecular and cellular biology 40 12771511
2002 Human surfactant protein D (SP-D) binds Mycoplasma pneumoniae by high affinity interactions with lipids. The Journal of biological chemistry 39 11916969
2013 Ligands and receptors of lung surfactant proteins SP-A and SP-D. Frontiers in bioscience (Landmark edition) 37 23747872
2007 The immunoregulatory roles of lung surfactant collectins SP-A, and SP-D, in allergen-induced airway inflammation. Immunobiology 37 17544824
2001 SP-D and GM-CSF regulate surfactant homeostasis via distinct mechanisms. American journal of physiology. Lung cellular and molecular physiology 37 11504698
2013 Lung surfactant protein D (SP-D) response and regulation during acute and chronic lung injury. Lung 36 23435873
2006 Surfactant protein D of the innate immune defence is inversely associated with human obesity and SP-D deficiency infers increased body weight in mice. Scandinavian journal of immunology 36 17083619
2002 Reversibility of pulmonary abnormalities by conditional replacement of surfactant protein D (SP-D) in vivo. The Journal of biological chemistry 36 12163500
2020 Exogenous pulmonary surfactant: A review focused on adjunctive therapy for severe acute respiratory syndrome coronavirus 2 including SP-A and SP-D as added clinical marker. Current opinion in colloid & interface science 35 33390762
2017 Morphology and molecular characterization of Demidospermus spirophallus n. sp., D. prolixus n. sp. (Monogenea: Dactylogyridae) and a redescription of D. anus in siluriform catfish from Brazil. Journal of helminthology 35 28382887
2012 Linking surfactant protein SP-D and IL-13: implications in asthma and allergy. Molecular immunology 35 23220073
2002 Structural requirements for SP-D function in vitro and in vivo: therapeutic potential of recombinant SP-D. Immunobiology 35 12396020
2015 DNA vaccine molecular adjuvants SP-D-BAFF and SP-D-APRIL enhance anti-gp120 immune response and increase HIV-1 neutralizing antibody titers. Journal of virology 34 25631080
2010 SP-D and regulation of the pulmonary innate immune system in allergic airway changes. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 34 20447075
2004 High resolution mass spectrometric alveolar proteomics: identification of surfactant protein SP-A and SP-D modifications in proteinosis and cystic fibrosis patients. Proteomics 34 15274124
2002 Lung surfactant protein D (SP-D) and the molecular diverted descendants: conglutinin, CL-43 and CL-46. Immunobiology 34 12396011
2012 MMP-9 cleaves SP-D and abrogates its innate immune functions in vitro. PloS one 33 22860023
2016 YKL-40, CCL18 and SP-D predict mortality in patients hospitalized with community-acquired pneumonia. Respirology (Carlton, Vic.) 32 27782361
1999 Recombinant SP-D carbohydrate recognition domain is a chemoattractant for human neutrophils. The American journal of physiology 32 9887065
2018 Oxidative damage of SP-D abolishes control of eosinophil extracellular DNA trap formation. Journal of leukocyte biology 31 29733456
2006 Contributions of phenylalanine 335 to ligand recognition by human surfactant protein D: ring interactions with SP-D ligands. The Journal of biological chemistry 31 16636058
2016 Surfactant Proteins SP-A and SP-D Ameliorate Pneumonia Severity and Intestinal Injury in a Murine Model of Staphylococcus Aureus Pneumonia. Shock (Augusta, Ga.) 30 26849628
2009 Multimeric and trimeric subunit SP-D are interconvertible structures with distinct ligand interaction. Molecular immunology 30 19577304
2009 The human lung surfactant proteins A (SP-A) and D (SP-D) interact with apoptotic target cells by different binding mechanisms. Immunobiology 30 19880212
1991 Surfactant protein D (SP-D) counteracts the inhibitory effect of surfactant protein A (SP-A) on phospholipid secretion by alveolar type II cells. Interaction of native SP-D with SP-A. The Biochemical journal 30 1930130
2006 SP-D-deficient mice are resistant to hyperoxia. American journal of physiology. Lung cellular and molecular physiology 28 17158597
2019 Evaluation of the Diagnostic Efficacies of Serological Markers KL-6, SP-A, SP-D, CCL2, and CXCL13 in Idiopathic Interstitial Pneumonia. Respiration; international review of thoracic diseases 27 31665737
2011 Assessment of the antiviral properties of recombinant porcine SP-D against various influenza A viruses in vitro. PloS one 26 21935489
2009 Elevated plasma surfactant protein D (SP-D) levels and a direct correlation with anti-severe acute respiratory syndrome coronavirus-specific IgG antibody in SARS patients. Scandinavian journal of immunology 26 19439011
2008 Association of polymorphisms in the human surfactant protein-D (SFTPD) gene and postnatal pulmonary adaptation in the preterm infant. Acta paediatrica (Oslo, Norway : 1992) 26 18785967
2007 Expression sites of the collectin SP-D suggest its importance in first line host defence: power of combining in situ hybridisation, RT-PCR and immunohistochemistry. Molecular immunology 26 17420052
2001 GM-CSF mediates alveolar macrophage proliferation and type II cell hypertrophy in SP-D gene-targeted mice. American journal of physiology. Lung cellular and molecular physiology 26 11350793
2022 Surfactant protein D (SP-D) as a biomarker of SARS-CoV-2 infection. Clinica chimica acta; international journal of clinical chemistry 24 36341812
2021 Serial Measurements of Circulating KL-6, SP-D, MMP-7, CA19-9, CA-125, CCL18, and Periostin in Patients with Idiopathic Pulmonary Fibrosis Receiving Antifibrotic Therapy: An Exploratory Study. Journal of clinical medicine 24 34501312
2012 Surfactant protein D (Sp-D) binds to membrane-proximal domain (D3) of signal regulatory protein α (SIRPα), a site distant from binding domain of CD47, while also binding to analogous region on signal regulatory protein β (SIRPβ). The Journal of biological chemistry 24 22511785
2011 SP-A1, SP-A2 and SP-D gene polymorphisms in severe acute respiratory syncytial infection in Chilean infants. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 24 21601013
2004 Binding and agglutination of Streptococcus pneumoniae by human surfactant protein D (SP-D) vary between strains, but SP-D fails to enhance killing by neutrophils. Infection and immunity 24 14742512
2018 Supramolecular Assembly of Human Pulmonary Surfactant Protein SP-D. Journal of molecular biology 23 29626540
2009 Genetic variants in surfactant, pulmonary-associated protein D (SFTPD) and Japanese susceptibility to ulcerative colitis. Inflammatory bowel diseases 22 19340882
2014 Surfactant protein SP-D modulates activity of immune cells: proteomic profiling of its interaction with eosinophilic cells. Expert review of proteomics 21 24697551
2013 Donor surfactant protein D (SP-D) polymorphisms are associated with lung transplant outcome. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 21 23841811
2010 Surfactant protein (SP)-A and SP-D as antimicrobial and immunotherapeutic agents. Recent patents on anti-infective drug discovery 21 20230362
2006 Neither SP-A nor NH2-terminal domains of SP-A can substitute for SP-D in regulation of alveolar homeostasis. American journal of physiology. Lung cellular and molecular physiology 21 16500946
2004 The genes encoding bovine SP-A, SP-D, MBL-A, conglutinin, CL-43 and CL-46 form a distinct collectin locus on Bos taurus chromosome 28 (BTA28) at position q.1.8-1.9. Animal genetics 21 15265076