Integrin molecules involved in lymphocyte homing to Peyer's patches.
This review summarizes experiments designed to analyze lymphocyte receptors mediating recognition of and adhesion to HEV in mucosal lymphoid organs. A monoclonal antibody (R1-2) was selected which inhibits the adhesion of murine lymphocytes to Peyer's patch HEV. Antibody R1-2 recognizes the alpha chain (alpha 4m) of the murine lymphocyte cell-surface alpha beta heterodimer LPAM-1. The association of LPAM-1 alpha and beta chains requires the presence of Ca++ ions. Two proteins of Mr 84,000 and 62,000 which are also precipitated by antibody R1-2 most likely represent fragments of alpha 4m. The cross-reactivity of a monospecific rabbit anti-serum indicated that alpha 4m is analogous to the alpha chain of the human integrin molecule VLA-4. In addition, a cDNA clone encoding the human VLA-4 alpha chain hybridized with RNA from alpha 4m+ but not alpha 4m- cell lines. However, the LPAM-1 beta subunit (beta p) was shown to be immunochemically and biochemically distinct from integrin beta 1, beta 2, and beta 3, indicating that beta p represents a unique integrin beta chain. When the beta subunits associated with alpha 4m on a panel of lymphoma cell lines were analyzed, it was found that, depending on the cellular source, alpha 4m can associate with either of two beta chains: beta p or integrin beta 1. Therefore alpha 4m appears to be the common subunit of the two lymphocyte cell surface heterodimers LPAM-1 (alpha 4m/beta p) and LPAM-2 (alpha 4m/beta 1). LPAM-2 is analogous to the human VLA-4 molecule, whereas LPAM-1 represents a unique integrin heterodimer. Antibody R1-2 inhibited Peyer's patch HEV-adhesion of normal mouse lymphocytes and every lymphoma cell line tested including LPAM-1 and LPAM-2 single-positive cell lines. We also showed that the binding capacity of variants of a clonal lymphoma cell line to Peyer's patch HEV correlates with the level of LPAM-1 expression. It therefore appears that both heterodimers are involved in lymphocyte-Peyer's patch HEV interactions and that the adhesion of lymphocytes to Peyer's patch HEV is generally LPAM-1- or LPAM-2-dependent. We further investigated whether VLA-4, the human analog of LPAM-2, can mediate adhesion of human lymphocytes to HEV in mucosal lymphoid organs.(ABSTRACT TRUNCATED AT 400 WORDS)
Holzmann
B
B
Department of Pathology, Stanford University Medical School, California 94305.
Weissman
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IL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology* / Q000502:physiology; D000954:Antigens, Surface / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002465:Cell Movement; D004730:Endothelium, Vascular / Q000502:physiology; D006801:Humans; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D008214:Lymphocytes / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D015394:Molecular Structure; D009928:Organ Specificity; D010581:Peyer's Patches / Q000502:physiology*; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000502:physiology; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen; D002118:Calcium