Role of integrin alpha 4 beta 7/alpha 4 beta P in lymphocyte adherence to fibronectin and VCAM-1 and in homotypic cell clustering

Integrins are heterodimeric cell surface proteins that mediate both cell-cell and cell-extracellular matrix interactions. We and others recently identified cDNAs encoding a novel integrin beta subunit, beta 7, in lymphocytes. We have now detected beta 7 mRNA in mouse TK-1 T lymphoma cells, which are known to express the putative Peyer's patch homing receptor alpha 4 beta P. We used an anti-peptide antiserum and a novel mAb against the beta 7 subunit to show that TK-1 cells express beta 7 as the only subunit associated with alpha 4. We conclude that beta 7 and beta P are identical. We also show that activated peripheral blood T cells express alpha 4 beta 7. We studied the function of alpha 4 beta 7/alpha 4 beta P in TK-1 cells, which do not express very late antigen (VLA)-4 (alpha 4 beta 1). Cells adhered to intact fibronectin and to a fibronectin fragment containing the CS-1 region, but not to a fragment containing the RGD sequence. Adhesion to fibronectin was inhibited by antibodies to alpha 4, suggesting that alpha 4 beta 7 is a fibronectin receptor. We confirmed that alpha 4 beta 7 binds to the CS- 1 region of fibronectin using affinity chromatography. TK-1 cell adhesion to the vascular cell adhesion molecule VCAM-1 was also inhibited by antibodies to alpha 4, implying that alpha 4 beta 7 also plays a role in the adherence of lymphocytes to endothelial cells. TK-1 cell binding to fibronectin and VCAM-1 is markedly increased by brief PMA stimulation. We also found that mAbs against alpha 4 and beta 7 induce homotypic clustering of TK-1 cells. Taken together these results suggest that alpha 4 beta 7/alpha 4 beta P recognizes some or all of the same widely distributed ligands recognized by VLA-4 (alpha 4 beta 1) and that the role of alpha 4 beta 7/alpha 4 beta P may not be restricted to lymphocyte homing.

[1]  J D Chambers,et al.  Two-step model of leukocyte-endothelial cell interaction in inflammation: distinct roles for LECAM-1 and the leukocyte beta 2 integrins in vivo. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[2]  C. Benjamin,et al.  Expression and functional characterization of a soluble form of vascular cell adhesion molecule 1. , 1991, Biochemical and biophysical research communications.

[3]  P. Kincade,et al.  A VCAM-like adhesion molecule on murine bone marrow stromal cells mediates binding of lymphocyte precursors in culture , 1991, The Journal of cell biology.

[4]  T. Springer,et al.  Leukocytes roll on a selectin at physiologic flow rates: Distinction from and prerequisite for adhesion through integrins , 1991, Cell.

[5]  J. Watson,et al.  Identity between the novel integrin beta 7 subunit and an antigen found highly expressed on intraepithelial lymphocytes in the small intestine. , 1991, Biochemical and biophysical research communications.

[6]  I. Weissman,et al.  Evidence for a role of the integrin VLA-4 in lympho-hemopoiesis , 1991, The Journal of experimental medicine.

[7]  C. Smith,et al.  The peripheral lymph node homing receptor, LECAM-1, is involved in CD18-independent adhesion of human neutrophils to endothelium. , 1991, Biochemical and biophysical research communications.

[8]  L. Picker,et al.  Differential expression of homing-associated adhesion molecules by T cell subsets in man. , 1990, Journal of immunology.

[9]  P. Kilshaw,et al.  A new surface antigen on intraepithelial lymphocytes in the intestine , 1990, European journal of immunology.

[10]  T. Carlos,et al.  Vascular cell adhesion molecule-1 mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells. , 1990, Blood.

[11]  Timothy A. Springer,et al.  Adhesion receptors of the immune system , 1990, Nature.

[12]  K. Miyake,et al.  Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition , 1990, The Journal of experimental medicine.

[13]  F. Sánchez‐Madrid,et al.  An alternative leukocyte homotypic adhesion mechanism, LFA-1/ICAM-1- independent, triggered through the human VLA-4 integrin , 1990, The Journal of cell biology.

[14]  W. Carter,et al.  Human B lymphocytes define an alternative mechanism of adhesion to fibronectin. The interaction of the alpha 4 beta 1 integrin with the LHGPEILDVPST sequence of the type III connecting segment is sufficient to promote cell attachment. , 1990, Journal of immunology.

[15]  H. Stein,et al.  The HML-1 antigen of intestinal lymphocytes is an activation antigen. , 1990, Journal of immunology.

[16]  K. Horgan,et al.  Roles of Adhesion Molecules in T‐Cell Recognition: Fundamental Similarities between Four Integrins on Resting Human T Cells (LFA‐1, VLA‐4, VLA‐5, VLA‐6) in Expression, Binding, and Costimulation , 1990, Immunological reviews.

[17]  M. Humphries,et al.  Affinity chromatographic isolation of the melanoma adhesion receptor for the IIICS region of fibronectin and its identification as the integrin alpha 4 beta 1. , 1990, The Journal of biological chemistry.

[18]  M. Elices,et al.  VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/Fibronectin binding site , 1990, Cell.

[19]  B. McIntyre,et al.  A monoclonal antibody to VLA-4 alpha-chain (CDw49d) induces homotypic lymphocyte aggregation. , 1990, Journal of immunology.

[20]  Michael L. Dustin,et al.  T-cell receptor cross-linking transiently stimulates adhesiveness through LFA-1 , 1989, Nature.

[21]  E. Berg,et al.  Neutrophil Mac-1 and MEL-14 adhesion proteins inversely regulated by chemotactic factors. , 1989, Science.

[22]  W. Carter,et al.  Identification and characterization of the T lymphocyte adhesion receptor for an alternative cell attachment domain (CS-1) in plasma fibronectin , 1989, The Journal of cell biology.

[23]  I. Weissman,et al.  Peyer's patch‐specific lymphocyte homing receptors consist of a VLA‐4‐like alpha chain associated with either of two integrin beta chains, one of which is novel. , 1989, The EMBO journal.

[24]  M. Elices,et al.  The primary structure of the alpha 4 subunit of VLA‐4: homology to other integrins and a possible cell‐cell adhesion function. , 1989, The EMBO journal.

[25]  L. Stoolman.  Adhesion molecules controlling lymphocyte migration , 1989, Cell.

[26]  M. Hayashi,et al.  Novel purification of vitronectin from human plasma by heparin affinity chromatography. , 1988, Cell structure and function.

[27]  J. Strominger,et al.  Characterization of the cell surface heterodimer VLA-4 and related peptides. , 1987, The Journal of biological chemistry.

[28]  Richard O. Hynes,et al.  Integrins: A family of cell surface receptors , 1987, Cell.

[29]  T. Springer,et al.  The requirement for lymphocyte function-associated antigen 1 in homotypic leukocyte adhesion stimulated by phorbol ester , 1986, The Journal of experimental medicine.

[30]  E. Ruoslahti,et al.  Identification and isolation of a 140 kd cell surface glycoprotein with properties expected of a fibronectin receptor , 1985, Cell.

[31]  K. A. Wall,et al.  Cloned T Lymphocytes and Monoclonal Antibodies as Probes for Cell Surface Molecules Active in T Cell‐Mediated Cytolysis , 1982, Immunological reviews.

[32]  E. Engvall,et al.  Binding of soluble form of fibroblast surface protein, fibronectin, to collagen , 1977, International journal of cancer.

[33]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[34]  R. Kofler.  Mouse macrophage beta subunit (CD11b) cDNA for the CR3 complement receptor/Mac-1 antigen. , 1991, Immunogenetics.

[35]  E. Berg.  CHAPTER 6 – Vascular Addressins: Tissue Selective Endothelial Cell Adhesion Molecules for Lymphocyte Homing , 1991 .

[36]  D. Sheppard,et al.  Novel integrin alpha and beta subunit cDNAs identified in airway epithelial cells and lung leukocytes using the polymerase chain reaction. , 1991, American journal of respiratory cell and molecular biology.

[37]  M. Hemler,et al.  Functional evidence for three distinct and independently inhibitable adhesion activities mediated by the human integrin VLA-4. Correlation with distinct alpha 4 epitopes. , 1991, The Journal of biological chemistry.

[38]  R. Hynes,et al.  Lymphoid cells recognize an alternatively spliced segment of fibronectin via the integrin receptor alpha 4 beta 1. , 1990, Cell.

[39]  M. Hemler.  VLA proteins in the integrin family: structures, functions, and their role on leukocytes. , 1990, Annual review of immunology.

[40]  E. Butcher.  Warner-Lambert/Parke-Davis Award lecture. Cellular and molecular mechanisms that direct leukocyte traffic. , 1990, The American journal of pathology.

[41]  K. Horgan,et al.  Regulated expression and binding of three VLA (beta 1) integrin receptors on T cells. , 1990, Nature.

[42]  J. Watson,et al.  Cloning and sequence analysis of a novel beta 2-related integrin transcript from T lymphocytes: homology of integrin cysteine-rich repeats to domain III of laminin B chains. , 1990, International immunology.

[43]  I. Weissman,et al.  Identification of a murine Peyer's patch--specific lymphocyte homing receptor as an integrin molecule with an alpha chain homologous to human VLA-4 alpha. , 1989, Cell.

[44]  C. Griscelli,et al.  A monoclonal antibody (HML‐1) defining a novel membrane molecule present on human intestinal lymphocytes , 1987, European journal of immunology.

[45]  F. Sánchez‐Madrid,et al.  VLA‐3: A novel polypeptide association within the VLA molecular complex: cell distribution and biochemical characterization , 1986, European journal of immunology.

[46]  I. Goldstein,et al.  Adherence of human polymorphonuclear leukocytes to endothelial monolayers: effects of temperature, divalent cations, and chemotactic factors on the strength of adherence measured with a new centrifugation assay. , 1985, Blood.