Alpha 4 beta 7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1.
The mucosal vascular addressin, MAdCAM-1, is an immunoglobulin superfamily adhesion molecule for lymphocytes that is expressed by mucosal venules and helps direct lymphocyte traffic into Peyer's patches (PP) and the intestinal lamina propria. We demonstrate that the lymphocyte integrin alpha 4 beta 7, also implicated in homing to PP, is a receptor for MAdCAM-1. Certain antibodies to alpha 4 and beta 7 integrin chains but not to the beta 2 integrin LFA-1 inhibit lymphocyte binding to purified MAdCAM-1 and to MAdCAM-1 transfectants. Lymph node lymphocytes, alpha 4 beta 7+ TK1 lymphoma cells, and a beta 7-transfected variant of an alpha 4+ B cell line, 38C13, bind constitutively to MAdCAM-1. Binding is enhanced by Mn(++)-induced integrin activation. The related integrin alpha 4 beta 1 supports efficient binding to VCAM-1 but not to MAdCAM-1, even after integrin activation, indicating that MAdCAM-1 is a preferential ligand for alpha 4 beta 7. Alpha 4 beta 7 can also bind VCAM-1, but this requires greater integrin activation than binding to MAdCAM-1. The findings imply a selective role for the interaction of alpha 4 beta 7 and MAdCAM-1 lymphocyte in homing to mucosal sites.
Berlin
C
C
Department of Pathology, Stanford University, California 94305.
Berg
E L
EL
Briskin
M J
MJ
Andrew
D P
DP
Kilshaw
P J
PJ
Holzmann
B
B
Weissman
I L
IL
Hamann
A
A
Butcher
E C
EC
D000818:Animals; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D039041:Integrin alpha4beta1; D039641:Integrin beta Chains; D016023:Integrins / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D009088:Mucoproteins / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039041:Integrin alpha4beta1; D039641:Integrin beta Chains; D016023:Integrins; C504265:MADCAM1 protein, human; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D019010:Vascular Cell Adhesion Molecule-1; C091368:integrin beta7