Expression and function of the MAdCAM-1 receptor, integrin alpha 4 beta 7, on human leukocytes.
Recirculation of mouse lymphocytes to the gut involves binding of the lymphocyte integrin alpha 4 beta 7 to the mucosal vascular addressin, MAdCAM-1. In humans, indirect evidence suggests that CD4+ T cells that express high levels of alpha 4 beta 7 migrate selectively to the gut. We now report that human adult blood CD8+ T cells and B cells, like CD4+ T cells, have heterogeneous expression of alpha 4 beta 7. In contrast, NK cells, eosinophils, and newborn blood T and B cells have relatively homogeneous expression of alpha 4 beta 7. CD4+ and CD8+ T cell expression of alpha 4 beta 7 was related to age, CD45RA expression, and integrin beta 1 (CD29) expression, suggesting that alpha 4 beta 7 expression changes after primary activation of CD4+ and CD8+ T cells in vivo. To directly determine whether human alpha 4 beta 7 mediates adhesion to MAdCAM-1, we performed in vitro adhesion assays with two alpha 4 beta 7+ human lymphoma cell lines. The results indicate that human alpha 4 beta 7 is a receptor for MAdCAM-1, whereas alpha 4 beta 1 is not. Adhesion of HUT 78 cells to MAdCAM-1 required Mn2+, whereas adhesion of RPMI 8866 cells did not, suggesting that alpha 4 beta 7 may have at least two distinct functional states. The ability of lymphocytes to bind to MAdCAM-1 and recirculate to mucosal organs is likely to be influenced both by the level of alpha 4 beta 7 expression and by the functional state of the alpha 4 beta 7 molecule.
Erle
D J
DJ
Department of Medicine, University of California, San Francisco 94143.
Briskin
M J
MJ
Butcher
E C
EC
Garcia-Pardo
A
A
Lazarovits
A I
AI
Tidswell
M
M
D000328:Adult; D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002460:Cell Line; D006801:Humans; D007136:Immunoglobulins / Q000502:physiology*; D019012:Integrin beta1; D016023:Integrins / Q000032:analysis / Q000502:physiology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008214:Lymphocytes / Q000502:physiology*; D008345:Manganese / Q000494:pharmacology; D051379:Mice; D009088:Mucoproteins / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000502:physiology*
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D019012:Integrin beta1; D016023:Integrins; C504265:MADCAM1 protein, human; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D016201:Receptors, Lymphocyte Homing; D008345:Manganese; D017493:Leukocyte Common Antigens