Affinage

MADCAM1

Mucosal addressin cell adhesion molecule 1 · UniProt Q13477

Length
382 aa
Mass
40.2 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAdCAM-1 is an endothelial immunoglobulin superfamily adhesion molecule that directs tissue-selective lymphocyte, dendritic cell, and hematopoietic progenitor homing to gut-associated lymphoid tissues and bone marrow through its role as the dominant ligand for integrin α4β7. Its two N-terminal Ig domains present a critical Asp42 residue in the CD loop of domain 1 and an accessory negatively charged β-ribbon in the DE loop of domain 2, which together form a bipartite α4β7-binding surface whose engagement supports tethering, rolling, and firm adhesion under shear flow; the mucin-like domain, when decorated with GlcNAc6ST-1-dependent sulfated sialyl carbohydrates, additionally serves as a facultative L-selectin ligand (PMID:7687523, PMID:9655832, PMID:7505053, PMID:19067429). MAdCAM-1 transcription is driven by NF-κB (activated downstream of TNF-α via MAPK and AT1R signaling) and the homeodomain factor NKX2.3, whose genetic ablation eliminates mucosal MAdCAM-1 expression and disrupts lymphocyte compartmentalization (PMID:10790368, PMID:11546645, PMID:19940029). Chemokines CCL25, CCL28, and CCL21 presented on the endothelial surface rapidly trigger α4β7-dependent arrest on MAdCAM-1 through Gi-coupled signaling, and blockade of the α4β7–MAdCAM-1 axis reduces intestinal inflammation, hepatic steatohepatitis, and impairs hematopoietic stem cell engraftment in bone marrow transplantation models (PMID:18308860, PMID:9670974, PMID:28192190, PMID:26422691).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1993 High

    Identification of α4β7 integrin as the specific lymphocyte receptor for MAdCAM-1 established the molecular basis for mucosal-selective lymphocyte adhesion, resolving how MAdCAM-1 functions distinctly from VCAM-1.

    Evidence Cell adhesion assays with purified MAdCAM-1, blocking antibodies against α4, β7, β2 chains, and Mn2+ activation using lymphoma cell lines

    PMID:7687523

    Open questions at the time
    • Structural basis of α4β7 versus α4β1 selectivity not yet defined
    • In vivo relevance of preferential binding not demonstrated
  2. 1993 High

    Molecular cloning and biochemical characterization revealed MAdCAM-1 as a dual-function molecule — its Ig domains bind integrins while its mucin domain presents carbohydrates for L-selectin, explaining how a single endothelial molecule can mediate both selectin-dependent rolling and integrin-dependent arrest.

    Evidence cDNA cloning with COS cell expression and binding assays; parallel shear-flow adhesion assays with L-selectin transfectants and N-glycanase-treated MAdCAM-1 purified from mesenteric lymph nodes

    PMID:7505053 PMID:8502297

    Open questions at the time
    • Carbohydrate modifications responsible for L-selectin binding not molecularly defined
    • In vivo contribution of mucin domain versus Ig domains to homing not separated
  3. 1995 Medium

    Genomic characterization revealed tandem NF-κB sites in the MAdCAM-1 promoter, providing the first mechanistic link between inflammatory signaling and MAdCAM-1 transcriptional induction.

    Evidence Genomic cloning, sequencing, and 5′ promoter analysis of MAdCAM-1 gene (5 exons, chromosome 10)

    PMID:7650378

    Open questions at the time
    • NF-κB sites not yet validated by reporter or ChIP assays
    • Alternative splicing functional consequences unknown
  4. 1996 High

    Cloning of human MAdCAM-1 confirmed conservation of α4β7 binding via two N-terminal Ig domains and established mucosal-restricted expression, while showing loss of the IgA-like third domain — demonstrating species-specific structural variation.

    Evidence Functional expression cloning from macaque/human libraries, adhesion assays, RT-PCR tissue panel

    PMID:8609404

    Open questions at the time
    • Functional consequence of missing IgA domain in humans not determined
  5. 1997 High

    Systematic mutagenesis and chimera studies defined the bipartite integrin-binding surface: the LDT/Asp42 motif in the CD loop of Ig domain 1 is essential, while flanking structural context (including Ig domain 2) determines α4β7 versus α4β1 selectivity.

    Evidence Site-directed mutagenesis, VCAM-1/MAdCAM-1 chimera construction, and cell adhesion assays; parallel β7/β1 chimera mapping of integrin MIDAS-like domain

    PMID:9233649 PMID:9235944 PMID:9379078

    Open questions at the time
    • Atomic-resolution view of integrin–MAdCAM-1 interface not yet available
    • Role of each Ig domain in activation-state-dependent binding not dissected
  6. 1998 High

    The crystal structure of MAdCAM-1 Ig domains 1–2 at 2.2 Å resolution revealed how Asp42 is stabilized by buried Arg70 and identified the unusual DE-loop β-ribbon of domain 2 as a second integrin-contact surface, explaining mutagenesis data and the 8 Å displacement of the critical aspartate relative to VCAM-1.

    Evidence X-ray crystallography at 2.2 Å resolution with structural comparison to VCAM-1

    PMID:9655832

    Open questions at the time
    • No co-crystal with α4β7; exact integrin–ligand interface still modeled
    • Revised crystal form later raised questions about edge-strand assignment (PMID:11807247)
  7. 1998 Medium

    Demonstration that MAdCAM-1 costimulates T cell proliferation exclusively through α4β7 (not α4β1) and that chemokine CCL21 rapidly triggers α4β7-dependent arrest on MAdCAM-1 under flow established MAdCAM-1 as an active participant in lymphocyte activation and chemokine-directed adhesion cascades.

    Evidence T cell proliferation assays with immobilized Fc chimeras and blocking antibodies; flow chamber adhesion assays with pertussis toxin inhibition

    PMID:9670974 PMID:9842903

    Open questions at the time
    • Costimulatory signaling pathway downstream of α4β7 not characterized
    • Range of chemokines capable of triggering MAdCAM-1 arrest incompletely surveyed
  8. 2000 High

    Genetic ablation of NKX2.3 eliminated MAdCAM-1 expression in mucosal lymphoid tissue and disrupted lymphocyte compartmentalization, establishing NKX2.3 as a master transcriptional regulator of tissue-selective MAdCAM-1 expression.

    Evidence NKX2.3 knockout mice, immunohistochemistry, RT-PCR, transcriptional activation assays

    PMID:10790368 PMID:10926756

    Open questions at the time
    • Whether NKX2.3 directly binds the MAdCAM-1 promoter (ChIP) not shown
    • Relationship between NKX2.3 and NF-κB in MAdCAM-1 regulation not addressed
  9. 2001 Medium

    TNF-α–induced MAdCAM-1 expression was shown to require convergent MAPK and NF-κB/PARP signaling in endothelial cells, and MAdCAM-1 was found to localize to endothelial junctions — connecting inflammatory cytokine signaling to adhesion molecule positioning for leukocyte transmigration.

    Evidence RT-PCR, Western blotting, pharmacological kinase inhibitors in bEND.3 and SVEC endothelial cells, immunofluorescence

    PMID:11546645

    Open questions at the time
    • PARP role in NF-κB-dependent MAdCAM-1 transcription not mechanistically detailed
    • Junction localization functional consequences not tested
  10. 2001 Medium

    MAdCAM-1 expression during fetal life is widespread rather than mucosal-restricted, with postnatal restriction occurring as PNAd/L-selectin pathways replace α4β7/MAdCAM-1 in peripheral lymph nodes — redefining MAdCAM-1 as a developmentally regulated pan-lymphoid adhesion molecule.

    Evidence Immunostaining and functional binding assays on human fetal and pediatric tissues with blocking antibodies

    PMID:11606499

    Open questions at the time
    • Signals driving postnatal downregulation of MAdCAM-1 in peripheral nodes not identified
    • Functional consequences of fetal widespread expression not tested in vivo
  11. 2004 Medium

    α4β7/MAdCAM-1 interaction was shown to mediate hematopoietic progenitor cell tethering and rolling in bone marrow by intravital microscopy, extending MAdCAM-1 function beyond mucosal lymphocyte homing to hematopoietic stem cell engraftment.

    Evidence Intravital microscopy of bone marrow, in vivo homing assays with MAdCAM-1-blocking antibodies, CXCL12-stimulated adhesion assays

    PMID:15161666

    Open questions at the time
    • Relative contribution of MAdCAM-1 versus VCAM-1 in BM homing not fully quantified
    • Whether MAdCAM-1 is constitutive or induced on BM endothelium under homeostasis unclear
  12. 2009 Medium

    Two advances refined MAdCAM-1 regulation and function: GlcNAc6ST-1 was identified as the sulfotransferase that preferentially modifies MAdCAM-1 to generate L-selectin ligand carbohydrates, and AT1R was shown to regulate TNF-α-induced MAdCAM-1 expression via NF-κB nuclear translocation, linking the renin-angiotensin system to mucosal inflammation.

    Evidence Transfection of CHO cells co-expressing MAdCAM-1 with GlcNAc6ST enzymes, FACS, Western blotting; AT1R-/- mice and pharmacological blockade in DSS colitis model

    PMID:19067429 PMID:19940029

    Open questions at the time
    • Whether AT1R directly activates NF-κB or acts through intermediate kinases not resolved
    • In vivo contribution of GlcNAc6ST-1-modified MAdCAM-1 to L-selectin-dependent rolling not tested genetically
  13. 2011 Medium

    Mutagenesis of the CC' and DE loops showed that MAdCAM-1 engages different integrin activation states through distinct structural elements — the CC' loop/Asp42 is universally required, while the DE loop β-ribbon of domain 2 is dispensable for fully activated (Mn2+) but essential for physiologically activated α4β7.

    Evidence Site-directed mutagenesis of MAdCAM-1 CC' and DE loops, adhesion assays with Mn2+-, chemokine-, and talin-activated α4β7

    PMID:21296888

    Open questions at the time
    • No co-crystal structure of MAdCAM-1 with α4β7 in any activation state
    • How talin-induced versus Mn2+-induced conformational changes alter the integrin footprint on MAdCAM-1 not structurally resolved
  14. 2014 Medium

    MAdCAM-1/β7 axis was shown to govern intestinal localization of dendritic cells (both conventional and plasmacytoid), broadening MAdCAM-1's functional role beyond lymphocyte homing to innate immune cell positioning in the gut.

    Evidence MAdCAM-1 knockout and β7 integrin knockout mice, flow cytometry, migration assays

    PMID:25464027

    Open questions at the time
    • Specific integrin heterodimer on DCs mediating MAdCAM-1 binding not identified
    • Functional consequence of reduced gut DCs on mucosal immunity not assessed
  15. 2017 Medium

    MAdCAM-1 deficiency protected mice from diet-induced steatohepatitis by shifting immune balance toward regulatory T cells and anti-inflammatory macrophages, establishing MAdCAM-1 as a driver of hepatic inflammatory recruitment beyond its classical mucosal role.

    Evidence MAdCAM-1 and β7 knockout mice on high-fat and MCD diets, histomorphology, flow cytometry, oxidative stress markers

    PMID:28192190

    Open questions at the time
    • Whether hepatic MAdCAM-1 is endothelial or stromal in origin not determined
    • Mechanism linking MAdCAM-1 to Nrf2/HO-1 upregulation not elucidated
  16. 2022 Medium

    MAdCAM-1-expressing lymph node stromal cells were identified as early responders to immunization, and their age-dependent decline was shown to impair germinal center responses — revealing a non-endothelial, stromal role for MAdCAM-1+ cells in adaptive immunity.

    Evidence Heterochronic parabiosis, mouse immunization, bone marrow chimeras, flow cytometry

    PMID:35522725

    Open questions at the time
    • Whether MAdCAM-1 itself signals in stromal cells or merely marks them is unknown
    • TLR4-dependent mechanism of stromal cell activation not molecularly defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • A co-crystal structure of MAdCAM-1 bound to α4β7 integrin in physiological activation states is still lacking, and the signaling pathways downstream of MAdCAM-1 engagement in both endothelial and stromal cells remain undefined.
  • No atomic-resolution α4β7–MAdCAM-1 complex structure
  • Intracellular signaling triggered by MAdCAM-1 ligation in endothelial cells not characterized
  • How MAdCAM-1+ stromal cells contribute to germinal center formation mechanistically is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 4
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 2
Pathway
R-HSA-1500931 Cell-Cell communication 4 R-HSA-168256 Immune System 4
Partners
CHST2ITGA4ITGB7NKX2-3SELL

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Alpha 4 beta 7 integrin is a direct receptor for MAdCAM-1; antibodies to alpha 4 and beta 7 integrin chains (but not beta 2/LFA-1) inhibit lymphocyte binding to purified MAdCAM-1 and MAdCAM-1 transfectants; binding is enhanced by Mn2+-induced integrin activation; alpha 4 beta 7 preferentially binds MAdCAM-1 over VCAM-1, whereas alpha 4 beta 1 does not bind MAdCAM-1. Cell adhesion assays with purified MAdCAM-1 and MAdCAM-1 transfectants, blocking antibodies, Mn2+ activation, lymphoma cell lines Cell High 7687523
1993 MAdCAM-1 isolated from mesenteric lymph nodes (but not from cultured endothelioma cells) bears N-glycanase-resistant sialic acid-containing carbohydrate that supports adhesion of L-selectin-transfected lymphoid cells under shear, identifying MAdCAM-1 as a facultative ligand for L-selectin; interacting cells display selectin-dependent 'rolling' behaviour. Biochemical isolation of MAdCAM-1, adhesion assays under shear flow using L-selectin transfectants, N-glycanase treatment Nature High 7505053
1993 Molecular cloning revealed that MAdCAM-1 is an immunoglobulin superfamily member with two N-terminal Ig domains (homologous to ICAM-1 and VCAM-1) involved in integrin binding, a serine/threonine-rich mucin-like region that presents carbohydrate ligands for selectin binding, and a membrane-proximal domain homologous to IgA1 C-alpha2. cDNA cloning, transfection into COS cells, binding assay with mucosal HEV-binding T-cell lymphoma TK1, sequence analysis Nature High 8502297
1996 Human MAdCAM-1 has two N-terminal Ig-like domains that are functionally conserved for alpha 4 beta 7 binding but lacks the IgA-like third domain; human MAdCAM-1 selectively binds alpha 4 beta 7-expressing lymphocyte cell lines from both human and mouse; expression is restricted to mucosal tissues, gut-associated lymphoid tissues, and spleen. Functional expression cloning using macaque/human libraries, cell adhesion assays with alpha 4 beta 7+ lymphocyte lines, RT-PCR tissue expression analysis Journal of immunology High 8609404
1995 The MAdCAM-1 gene is located on chromosome 10, contains 5 exons encoding distinct functional domains (signal peptide, each Ig domain, mucin/IgA domain, transmembrane/cytoplasmic), and an alternatively spliced variant lacking the mucin/IgA exon 4 exists; the 5' flanking region contains tandem NF-kB sites, AP-1, AP-2 binding sites, and an estrogen response element. Genomic cloning, RT-PCR, sequencing, chromosomal mapping, 5' promoter analysis Journal of immunology Medium 7650378
1997 Site-directed mutagenesis identified the LDT sequence in the CD loop of MAdCAM-1's first Ig domain as a critical binding motif for alpha 4 beta 7 integrin adhesion and cell activation. Site-directed mutagenesis of MAdCAM-1, cell adhesion assays Immunologic research Medium 9379078
1997 Alpha 4 integrin binding specificity for MAdCAM-1 versus VCAM-1 is determined not only by the critical aspartate in the CD loop, but also by accessory binding sites including an Ig domain 2 region; VCAM-1/MAdCAM-1 chimeras showed that the MAdCAM-1 adhesion motif in the context of VCAM-1 supports alpha 4 beta 1 binding, but the VCAM-1 motif in MAdCAM-1 context does not, implicating flanking structural determinants. VCAM-1/MAdCAM-1 chimera construction, recombinant protein cell adhesion assays, site-directed mutagenesis of VCAM-1 The Journal of biological chemistry High 9235944
1997 Beta 7 integrin residues 46-386 specify alpha 4 beta 7 binding to MAdCAM-1; a MIDAS-like domain (residues 176-250) is critical for MAdCAM-1 and E-cadherin adhesion, mapped by seven blocking antibodies; residues 46-149 contain a Mn2+-dependent activating epitope that promotes MAdCAM-1 binding. Beta 7/beta 1 chimeras, human/mouse/rat chimeric beta 7 subunits, antibody epitope mapping, adhesion assays Journal of immunology High 9233649
1998 Crystal structure of human MAdCAM-1 Ig domains 1 and 2 at 2.2 Å resolution reveals two integrin-recognition motifs: Asp42 in the CD loop of domain 1 (the key integrin-binding residue, stabilized by buried Arg70) and an unusual negatively charged beta ribbon extending from the D and E strands of domain 2, both on the same face; architectural differences in CD loops between MAdCAM-1 and VCAM-1 cause an 8 Å shift in the critical aspartate position. X-ray crystallography at 2.2 Å resolution, structural comparison Structure High 9655832
1998 MAdCAM-1 costimulates T cell proliferation exclusively through integrin alpha 4 beta 7 (not alpha 4 beta 1), whereas VCAM-1 and CS-1 peptide costimulate exclusively through alpha 4 beta 1; MAdCAM-1-Fc can synergize with and induce hyperresponsiveness to B7-2; costimulation occurs even when MAdCAM-1 is spatially distant from anti-CD3 ('remote' costimulation). T cell proliferation assays with immobilized Fc chimeras, blocking antibodies to specific integrin chains European journal of immunology Medium 9842903
1998 Secondary lymphoid-tissue chemokine (SLC/CCL21) immobilized on substrate rapidly activates alpha 4 beta 7-mediated lymphocyte adhesion to MAdCAM-1 under flow conditions through a pertussis toxin-sensitive (Gi-coupled) pathway; this effect is specific to SLC among CC chemokines tested. Flow chamber adhesion assays, pertussis toxin inhibition, blocking antibodies Journal of immunology Medium 9670974
2000 Transcription factor NKX2.3 directly activates MAdCAM-1 transcription; NKX2.3-deficient mice lack MAdCAM-1 expression in mucosa-associated lymphoid tissue and spleen, resulting in failure of lymphocyte migration and homing to correct compartments. Gene knockout (NKX2.3-/-) mice, immunohistochemistry, RT-PCR, transcriptional activation assays The EMBO journal High 10790368 10926756
2001 TNF-alpha induces MAdCAM-1 mRNA and protein in endothelial cells via tyrosine kinase, p42/44 MAPK, p38 MAPK, and NF-kB/PARP-dependent pathways; MEK-1/2 is activated by TNF-alpha within minutes and is dependent on TK and p42/44 MAPKs; MAdCAM-1 is frequently distributed to endothelial junctions both in vitro and in vivo. RT-PCR, Western blotting, pharmacological kinase inhibitors, immunofluorescence in endothelial cell lines (bEND.3 and SVEC) American journal of physiology. Cell physiology Medium 11546645
2001 MAdCAM-1 expressed on inflamed hepatic portal vein/sinusoidal endothelium in autoimmune liver disease is functionally active, supporting alpha 4 beta 7+ lymphocyte adhesion (inhibited by anti-MAdCAM-1, anti-alpha 4 beta 7, anti-alpha 4 antibodies) and rolling under flow conditions. Modified Stamper-Woodruff binding assays, flow-based adhesion assays, blocking antibodies on human tissue sections Hepatology Medium 11343233
1996 MAdCAM-1, VCAM-1, and ICAM-1 are expressed on choroid plexus epithelium (not endothelium) constitutively (ICAM-1, VCAM-1) or de novo during EAE (MAdCAM-1); these epithelial CAMs are locally synthesized and mediate lymphocyte binding via LFA-1 and alpha 4 integrin in Stamper-Woodruff assays, implicating the blood-CSF barrier epithelium in CNS immunosurveillance. Immunohistochemistry, in situ hybridization, cytokine stimulation of primary choroid plexus epithelial cells, Stamper-Woodruff binding assays The American journal of pathology Medium 8669469
2002 A revised crystal structure of human MAdCAM-1 Ig domains 1 and 2 shows one edge strand relocated to the opposite sheet compared with the first structure, altering the conformation of key integrin-binding residues; MAdCAM-1 forms dimers within the crystal lattice, suggesting oligomerization may influence biological function. X-ray crystallography (second crystal form), structural comparison Acta crystallographica. Section D, Biological crystallography Medium 11807247
2008 Immobilized CCL25 and CCL28 specifically trigger alpha 4 beta 7-dependent lymphocyte arrest on MAdCAM-1 under shear flow without affecting adhesion to VCAM-1; alpha 4 beta 7/MAdCAM-1 and alpha 4 beta 1/VCAM-1 operate as independent adhesion pathways; CCL21 and CXCL12 trigger a motile phenotype (lamellipodia/uropod) after arrest on MAdCAM-1. Flow-based adhesion assays, integrin-specific blocking antibodies, immobilized chemokines American journal of physiology. Gastrointestinal and liver physiology Medium 18308860
2009 GlcNAc6ST-1 preferentially utilizes MAdCAM-1 protein as a scaffold for GlcNAc-6-O-sulfation in L-selectin ligand carbohydrate biosynthesis; co-localization of MAdCAM-1 and L-selectin ligand carbohydrates (MECA-79 epitope) at luminal surface of HEV-like vessels was demonstrated, and UC disease activity correlates with GlcNAc6ST-1-mediated decoration rather than MAdCAM-1 protein levels per se. RT-PCR, immunofluorescence, FACS, Western blotting of CHO/Lec2 transfectants co-expressing MAdCAM-1 with GlcNAc6ST enzymes, immunohistochemistry Inflammatory bowel diseases Medium 19067429
2011 The CC' loop of MAdCAM-1 Ig domain 1 (including Asp-42) is indispensable for binding both low- and high-affinity alpha 4 beta 7; the DE loop of domain 2 is required for binding to inactive and SDF-1alpha/talin-activated alpha 4 beta 7 but is less critical for Mn2+-activated alpha 4 beta 7, indicating distinct conformational requirements for MAdCAM-1 binding to different integrin activation states. Site-directed mutagenesis of MAdCAM-1 CC' and DE loops, cell adhesion assays with Mn2+- or chemokine/talin-activated alpha 4 beta 7 The Journal of biological chemistry Medium 21296888
2004 Alpha 4 beta 7 on hematopoietic progenitor cells (HPCs) mediates tethering and rolling on MAdCAM-1 in bone marrow (demonstrated by intravital microscopy); blocking MAdCAM-1 significantly reduces HPC homing after bone marrow transplantation, contributing to approximately half of all alpha 4 integrin-mediated homing activity. Flow cytometry, CXCL12-stimulated adhesion to immobilized MAdCAM-1, BM intravital microscopy, homing assays with blocking antibodies Blood Medium 15161666
2009 Angiotensin II type 1 receptor (AT1R) regulates TNF-alpha-induced MAdCAM-1 expression via NF-kB nuclear translocation (but not p38 MAPK or IkB phosphorylation); AT1R-deficient mice show reduced MAdCAM-1 expression and attenuated DSS-induced colitis. AT1R blocker treatment and AT1R-/- mice, Western blotting, NF-kB translocation assays, DSS colitis model American journal of physiology. Gastrointestinal and liver physiology Medium 19940029
2014 MAdCAM-1 mediates intestinal localization of dendritic cells (conventional DCs and plasmacytoid DCs) via beta 7 integrin; MAdCAM-1-deficient and beta 7 integrin-deficient mice both show reduced CD11c+ cells and plasmacytoid DCs in gut epithelium, and reduced migration efficiency of pDC and cDC precursors into the intraepithelial compartment. MAdCAM-1 knockout mice, beta 7 integrin knockout mice, flow cytometry, migration assays Clinical immunology Medium 25464027
2015 Beta 7 integrin on hematopoietic stem cells (HSCs) interacts with MAdCAM-1 on bone marrow endothelial cells to promote HSC homing and engraftment; lethal irradiation induces MAdCAM-1 expression on BM endothelial cells; blocking MAdCAM-1 reduces HSC homing and impairs recipient survival; beta 7 KO HSCs have reduced CXCR4 expression and impaired migration. Flow cytometry, quantitative RT-PCR, in vivo homing assays, BM transplantation with blocking antibodies, beta 7 KO mice Stem cells and development Medium 26422691
2022 MAdCAM-1-expressing lymphoid stromal cells in lymph nodes are among the first cells to respond to immunization, proliferating and upregulating podoplanin and cell adhesion molecules; this response is abrogated in aged mice; TLR4 activation with adjuvants directly stimulates MAdCAM-1+ stromal cells (shown by bone marrow chimeras) and improves the germinal center response in both young and aged mice. Heterochronic parabiosis, mouse immunization, bone marrow chimeras, flow cytometry of MAdCAM-1+ stromal cells Science immunology Medium 35522725
2017 MAdCAM-1 promotes steatohepatitis development: MAdCAM-1-deficient mice show reduced hepatic inflammation, enhanced anti-oxidative stress (Nrf2, HO-1 upregulation), increased regulatory T cells and anti-inflammatory macrophages, and are protected from fibrosis initiation in high fat diet and methionine-choline-deficient diet models. MAdCAM-1 knockout mice, beta 7 integrin knockout mice, high fat diet / MCD diet models, histomorphology, flow cytometry, dihydroethidium staining Journal of hepatology Medium 28192190
1998 LPAM-1 (alpha 4 beta 7) binds to MAdCAM-1 and VCAM-1 via overlapping binding sites that overlap with the RGD recognition site; fibrinogen at physiological concentrations partially blocks TK-1 cell binding to MAdCAM-1, suggesting endogenous RGD-containing vascular proteins can compete with MAdCAM-1. Cell adhesion assays with RGD-containing peptides/polymers, fibrinogen competition, blocking antibodies European journal of immunology Medium 9541595
2001 In utero and during early childhood, MAdCAM-1 is widely expressed (not restricted to mucosal sites) and functionally governs lymphocyte adhesion to both gut and peripheral lymph node vessels via alpha 4 beta 7 integrin; after birth, MAdCAM-1 expression gradually becomes mucosal-restricted as PNAd/L-selectin interactions take over peripheral node adhesion. Immunostaining of human fetal and pediatric tissues, in vitro binding assays with blocking antibodies on tissue sections Gastroenterology Medium 11606499
2002 Exogenous NO donors (DETA-NO, SperNO) inhibit TNF-alpha-stimulated MAdCAM-1 expression in endothelial cells and reduce alpha 4 beta 7-dependent lymphocyte adhesion; inhibition of endogenous NO production (L-NAME, 1400W) does not induce or potentiate TNF-alpha-regulated MAdCAM-1 expression, distinguishing exogenous from endogenous NO regulation. Western blotting of MAdCAM-1 after NO donor/inhibitor pre-treatment, lymphocyte adhesion assays BMC gastroenterology Low 11481030
2004 P-selectin and MAdCAM-1 are co-expressed on maternal vessels during placenta development; long-term in vivo MAdCAM-1 blockade reduces recruitment of alpha 4 beta 7+ monocyte-like cells to the decidua, and absence of these cells is associated with reduced uterine NK cell numbers. In vivo antibody blockade, knockout mouse strains lacking specific adhesion receptors, immunohistochemistry European journal of immunology Medium 15484189

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1. Cell 1286 7687523
1993 L-selectin-mediated lymphocyte rolling on MAdCAM-1. Nature 477 7505053
1993 MAdCAM-1 has homology to immunoglobulin and mucin-like adhesion receptors and to IgA1. Nature 350 8502297
1994 Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on human leukocytes. Journal of immunology (Baltimore, Md. : 1950) 317 7517418
1997 Monoclonal antibodies specific for beta 7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) reduce inflammation in the colon of scid mice reconstituted with CD45RBhigh CD4+ T cells. Journal of immunology (Baltimore, Md. : 1950) 273 9036954
2001 MAdCAM-1 expressed in chronic inflammatory liver disease supports mucosal lymphocyte adhesion to hepatic endothelium (MAdCAM-1 in chronic inflammatory liver disease). Hepatology (Baltimore, Md.) 217 11343233
1996 ICAM-1, VCAM-1, and MAdCAM-1 are expressed on choroid plexus epithelium but not endothelium and mediate binding of lymphocytes in vitro. The American journal of pathology 203 8669469
2000 VCAM-1, but not ICAM-1 or MAdCAM-1, immunoblockade ameliorates DSS-induced colitis in mice. Laboratory investigation; a journal of technical methods and pathology 152 11045571
1995 Expression of the mucosal vascular addressin, MAdCAM-1, on sinus-lining cells in the spleen. The American journal of pathology 152 7677187
2006 Alpha-4 integrins and VCAM-1, but not MAdCAM-1, are essential for recruitment of mast cell progenitors to the inflamed lung. Blood 131 16670268
1999 Expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in acute and chronic inflammation. Journal of leukocyte biology 122 10080539
2002 Differential expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in ulcerative colitis and Crohn's disease. Pathology international 117 12100519
1998 Secondary lymphoid-tissue chemokine (SLC) stimulates integrin alpha 4 beta 7-mediated adhesion of lymphocytes to mucosal addressin cell adhesion molecule-1 (MAdCAM-1) under flow. Journal of immunology (Baltimore, Md. : 1950) 109 9670974
1996 Human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) demonstrates structural and functional similarities to the alpha 4 beta 7-integrin binding domains of murine MAdCAM-1, but extreme divergence of mucin-like sequences. Journal of immunology (Baltimore, Md. : 1950) 93 8609404
2006 Targeting mucosal addressin cellular adhesion molecule (MAdCAM)-1 to noninvasively image experimental Crohn's disease. Gastroenterology 88 16401463
1997 Involvement of beta 7 integrin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the development of diabetes in obese diabetic mice. Diabetes 86 9313747
1999 Expression of the mucosal vascular addressin, MAdCAM-1, in inflammatory liver disease. Liver 83 10661685
1996 Integrin alpha 4 beta 7 mediates human eosinophil interaction with MAdCAM-1, VCAM-1 and fibronectin. Immunology 79 8911148
2000 NKX2.3 is required for MAdCAM-1 expression and homing of lymphocytes in spleen and mucosa-associated lymphoid tissue. The EMBO journal 78 10790368
1997 Structure-function analysis of the integrin beta 7 subunit: identification of domains involved in adhesion to MAdCAM-1. Journal of immunology (Baltimore, Md. : 1950) 78 9233649
1997 Alpha4 integrin binding interfaces on VCAM-1 and MAdCAM-1. Integrin binding footprints identify accessory binding sites that play a role in integrin specificity. The Journal of biological chemistry 78 9235944
1995 Lymphocytes infiltrating the CNS during inflammation display a distinctive phenotype and bind to VCAM-1 but not to MAdCAM-1. International immunology 67 7540864
2004 Integrin alpha4beta7 and its counterreceptor MAdCAM-1 contribute to hematopoietic progenitor recruitment into bone marrow following transplantation. Blood 63 15161666
2004 The sphingosine-1-phosphate (S1P) lysophospholipid receptor S1P3 regulates MAdCAM-1+ endothelial cells in splenic marginal sinus organization. The Journal of experimental medicine 63 15583019
2008 CCL25 and CCL28 promote alpha4 beta7-integrin-dependent adhesion of lymphocytes to MAdCAM-1 under shear flow. American journal of physiology. Gastrointestinal and liver physiology 60 18308860
2001 Regulation and distribution of MAdCAM-1 in endothelial cells in vitro. American journal of physiology. Cell physiology 56 11546645
2000 Homeodomain factor Nkx2-3 controls regional expression of leukocyte homing coreceptor MAdCAM-1 in specialized endothelial cells of the viscera. Developmental biology 54 10926756
2018 Expression Patterns of TNFα, MAdCAM1, and STAT3 in Intestinal and Skin Manifestations of Inflammatory Bowel Disease. Journal of Crohn's & colitis 52 29182760
2011 Involvement of oxidative stress and mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in inflammatory bowel disease. Journal of clinical biochemistry and nutrition 51 21373262
2009 GlcNAc6ST-1-mediated decoration of MAdCAM-1 protein with L-selectin ligand carbohydrates directs disease activity of ulcerative colitis. Inflammatory bowel diseases 51 19067429
2005 Increased lymphocyte trafficking to colonic microvessels is dependent on MAdCAM-1 and C-C chemokine mLARC/CCL20 in DSS-induced mice colitis. Clinical and experimental immunology 51 15730387
2004 Blocking lymphotoxin-beta receptor activation diminishes inflammation via reduced mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expression and leucocyte margination in chronic DSS-induced colitis. Clinical and experimental immunology 51 15030510
1998 The structure of immunoglobulin superfamily domains 1 and 2 of MAdCAM-1 reveals novel features important for integrin recognition. Structure (London, England : 1993) 51 9655832
1998 Rat neutrophils express alpha4 and beta1 integrins and bind to vascular cell adhesion molecule-1 (VCAM-1) and mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Blood 50 9516132
2005 In vivo demonstration of T lymphocyte migration and amelioration of ileitis in intestinal mucosa of SAMP1/Yit mice by the inhibition of MAdCAM-1. Clinical and experimental immunology 49 15762871
1997 Mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Its binding motif for alpha 4 beta 7 and role in experimental colitis. Immunologic research 49 9379078
2020 Sialyltransferase inhibition leads to inhibition of tumor cell interactions with E-selectin, VCAM1, and MADCAM1, and improves survival in a human multiple myeloma mouse model. Haematologica 47 31101754
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