Mast cell–mediated inflammatory responses require the α2β1 integrin

Although the α2β1 integrin is widely expressed and has been extensively studied, it has not been previously implicated in mast cell biology. We observed that α2 integrin subunit-deficient mice exhibited markedly diminished neutrophil and interleukin-6 responses during Listeria monocytogenes – and zymosan-induced peritonitis. Since exudative neutrophils of wild-type mice expressed little α2β1 integrin, it seemed unlikely that this integrin mediated neutrophil migration directly. Here, we demonstrate constitutive α2β1 integrin expression on peritoneal mast cells. Although α2-null mice contain normal numbers of peritoneal mast cells, these α2-null cells do not support in vivo mast cell–dependent inflammatory responses. We conclude that α2β1 integrin provides a costimulatory function required for mast cell activation and cytokine production in response to infection.

[1]  M. Corr,et al.  The Role of FcγR Signaling in the K/B × N Serum Transfer Model of Arthritis1 , 2002, The Journal of Immunology.

[2]  O. Pertz,et al.  E-cadherin is a ligand for integrin α2β1 , 2002 .

[3]  Jinhua Lu,et al.  Collectins and ficolins: sugar pattern recognition molecules of the mammalian innate immune system. , 2002, Biochimica et biophysica acta.

[4]  C. Benoist,et al.  Mast Cells: A Cellular Link Between Autoantibodies and Inflammatory Arthritis , 2002, Science.

[5]  Y. Mekori,et al.  Heterotypic adhesion-induced mast cell activation: biologic relevance in the inflammatory context. , 2002, Molecular immunology.

[6]  S. Santoro,et al.  The alpha(2) integrin subunit-deficient mouse: a multifaceted phenotype including defects of branching morphogenesis and hemostasis. , 2002, The American journal of pathology.

[7]  S. Akira,et al.  Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity. , 2002, The Journal of clinical investigation.

[8]  B. Nieswandt,et al.  Integrin α2-Deficient Mice Develop Normally, Are Fertile, but Display Partially Defective Platelet Interaction with Collagen* , 2002, The Journal of Biological Chemistry.

[9]  M. Manns,et al.  Regulatory effects of stem cell factor and interleukin-4 on adhesion of human mast cells to extracellular matrix proteins. , 2002, Blood.

[10]  J. Marshall,et al.  Toll‐like receptor 4‐mediated activation of murine mast cells , 2001, Journal of leukocyte biology.

[11]  D. Friend,et al.  Intestinal Mast Cell Progenitors Require CD49dβ7 (α4β7 Integrin) for Tissue-specific Homing , 2001, The Journal of experimental medicine.

[12]  L. Bonewald,et al.  Composition of the extracellular matrix of the peritoneum. , 2001, Journal of the Society for Gynecologic Investigation.

[13]  A. Nakao,et al.  Protective Roles of Mast Cells Against Enterobacterial Infection Are Mediated by Toll-Like Receptor 41 , 2001, The Journal of Immunology.

[14]  L. Lanier,et al.  Cutting Edge: The Mouse NK Cell-Associated Antigen Recognized by DX5 Moncoclonal Antibody is CD49b (α2 Integrin, Very Late Antigen-2)1 , 2001, The Journal of Immunology.

[15]  T. Issekutz,et al.  Blockade of either alpha‐4 or beta‐7 integrins selectively inhibits intestinal mast cell hyperplasia and worm expulsion in response to Nippostrongylus brasiliensis infection , 2001, European journal of immunology.

[16]  W. Wallace,et al.  Differential Effects of CD18, CD29, and CD49 Integrin Subunit Inhibition on Neutrophil Migration in Pulmonary Inflammation1 , 2001, The Journal of Immunology.

[17]  B. Bochner,et al.  Acquisition and alteration of adhesion molecules during cultured human mast cell differentiation. , 2001, The Journal of allergy and clinical immunology.

[18]  B. Plytycz,et al.  Role of mast cells in zymosan‐induced peritoneal inflammation in Balb/c and mast cell‐deficient WBB6F1 mice , 2001, Journal of leukocyte biology.

[19]  S. Galli,et al.  A Role for CD21/CD35 and CD19 in Responses to Acute Septic Peritonitis: A Potential Mechanism for Mast Cell Activation1 , 2000, The Journal of Immunology.

[20]  G. Kollias,et al.  Mast Cells Control Neutrophil Recruitment during T Cell–Mediated Delayed-Type Hypersensitivity Reactions through Tumor Necrosis Factor and Macrophage Inflammatory Protein 2 , 2000, The Journal of experimental medicine.

[21]  J. Hales,et al.  Potent Costimulation of Effector T Lymphocytes by Human Collagen Type I1 , 2000, The Journal of Immunology.

[22]  M. Nishida,et al.  E-Cadherin and Cadherin-Associated Cytoplasmic Proteins Are Expressed in Murine Mast Cells , 2000, Laboratory Investigation.

[23]  E. Unanue,et al.  Immunity to Listeria infection. , 2000, Current opinion in immunology.

[24]  C. Potten,et al.  β7 integrin‐deficient mice: delayed leukocyte recruitment and attenuated protective immunity in the small intestine during enteric helminth infection , 2000, European journal of immunology.

[25]  V. Koteliansky,et al.  Regulation of inflammation by collagen-binding integrins α1β1 and α2β1 in models of hypersensitivity and arthritis , 2000 .

[26]  E. Ruoslahti,et al.  Integrin alpha(2)beta(1) (VLA-2) is a principal receptor used by neutrophils for locomotion in extravascular tissue. , 2000, Blood.

[27]  A. Grützkau,et al.  Adhesion of human mast cells to extracellular matrix provides a co‐stimulatory signal for cytokine production , 1999, Immunology.

[28]  P. A. van der Merwe,et al.  The mast cell tumor necrosis factor alpha response to FimH-expressing Escherichia coli is mediated by the glycosylphosphatidylinositol-anchored molecule CD48. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[29]  M. Perretti,et al.  Role of resident peritoneal macrophages and mast cells in chemokine production and neutrophil migration in acute inflammation: evidence for an inhibitory loop involving endogenous IL-10. , 1999, Journal of immunology.

[30]  T. Mayadas,et al.  Impaired mast cell development and innate immunity in Mac-1 (CD11b/CD18, CR3)-deficient mice. , 1998, Journal of immunology.

[31]  D. Metcalfe,et al.  Induction and enhancement of Fc(epsilon)RI-dependent mast cell degranulation following coculture with activated T cells: dependency on ICAM-1- and leukocyte function-associated antigen (LFA)-1-mediated heterotypic aggregation. , 1998, Journal of immunology.

[32]  D. Metcalfe,et al.  Activated T lymphocytes induce degranulation and cytokine production by human mast cells following cell‐to‐cell contact , 1998, Journal of leukocyte biology.

[33]  S. Galli,et al.  Impaired mast cell-dependent natural immunity in complement C3-deficient mice , 1997, Nature.

[34]  J. Apgar,et al.  Increased degranulation and phospholipase A2, C, and D activity in RBL cells stimulated through FcepsilonR1 is due to spreading and not simply adhesion. , 1997, Journal of cell science.

[35]  E. Bröcker,et al.  Heterotypic cell-cell adhesion of human mast cells to fibroblasts , 1997, Archives of Dermatological Research.

[36]  B. Echtenacher,et al.  Critical protective role of mast cells in a model of acute septic peritonitis , 1996, Nature.

[37]  S. Abraham,et al.  Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-α , 1996, Nature.

[38]  S. Santoro,et al.  The α2β1 Integrin: A Collagen Receptor on Platelets and other Cells , 1995, Thrombosis and Haemostasis.

[39]  H. Hashimoto,et al.  Expression and function of fibronectin binding integrins on rat mast cells. , 1995, International immunology.

[40]  S. Miyake,et al.  Identification of collagen and laminin receptor integrins on murine T lymphocytes , 1994, European journal of immunology.

[41]  Y. Kitamura,et al.  Two distinct types of cellular mechanisms in the development of delayed hypersensitivity in mice: requirement of either mast cells or macrophages for elicitation of the response. , 1993, Immunology.

[42]  C. Oliver,et al.  Adherence of rat basophilic leukemia (RBL-2H3) cells to fibronectin-coated surfaces enhances secretion. , 1992, Journal of immunology.

[43]  E. Kubista,et al.  Differential expression of cell surface integrins on human mast cells and human basophils , 1992, Annals of Hematology.

[44]  K. Austen,et al.  Differential expression of secretory granule proteases in mouse mast cells exposed to interleukin 3 and c-kit ligand , 1992, The Journal of experimental medicine.

[45]  D. Longo,et al.  Characterization and regulation of RB6-8C5 antigen expression on murine bone marrow cells. , 1991, Journal of immunology.

[46]  A. Capron,et al.  [3H]serotonin release: an improved method to measure mast cell degranulation. , 1978, Journal of immunological methods.

[47]  P. Taylor,et al.  J Soc Gynecol Investig , 2005 .

[48]  O. Pertz,et al.  E-cadherin is a ligand for integrin alpha2beta1. , 2002, Matrix biology : journal of the International Society for Matrix Biology.

[49]  M. Corr,et al.  The role of FcgammaR signaling in the K/B x N serum transfer model of arthritis. , 2002, Journal of immunology.

[50]  V. Koteliansky,et al.  Regulation of inflammation by collagen-binding integrins alpha1beta1 and alpha2beta1 in models of hypersensitivity and arthritis. , 2000, The Journal of clinical investigation.

[51]  M. Ginsberg,et al.  Integrins in the immune system. , 1999, Advances in immunology.

[52]  S. Santoro,et al.  The alpha 2 beta 1 integrin: a collagen receptor on platelets and other cells. , 1995, Thrombosis and haemostasis.

[53]  S. Santoro,et al.  Analysis of collagen receptors. , 1994, Methods in enzymology.

[54]  S. Santoro,et al.  [8] Analysis of collagen receptors , 1994 .

[55]  Y. Kitamura,et al.  Heterogeneity of mast cells and phenotypic change between subpopulations. , 1989, Annual review of immunology.