Distinct binding specificities of integrins alpha 4 beta 7 (LPAM-1), alpha 4 beta 1 (VLA-4), and alpha IEL beta 7.
Integrin receptors are important for regulating lymphocyte recirculation and recruitment to sites of inflammation. Transfectants of the B cell lymphoma 38C13 were generated that differ exclusively in the expression of integrin beta 1 or beta 7 subunits allowing for a functional comparison of lymphocyte Peyer's patch HEV adhesion molecule 1 (LPAM-1) (alpha 4 beta 7) and very late antigen 4 (VLA-4) (alpha 4 beta 1) in an identical cellular environment. Whereas 38-beta 7 transfectants bound to purified and cellular mucosal addressin cell adhesion molecule (MAdCAM-1), unstimulated 38-beta 1 cells failed to bind MAdCAM-1. Treatment of 38-beta 1 cells with Mn2+ but not with PMA induced low level binding to MAdCAM-1. MAdCAM-1 adhesion of 38-beta 7 cells was constitutive and not enhanced by Mn2+ treatment. Similarly, MAdCAM-1-dependent adhesion to mucosal high endothelial venules was shown for 38-beta 7 but not for 38-beta 1 cells. The results therefore establish the LPAM-1-MAdCAM-1 interaction as the functionally dominant adhesion pathway for regulating lymphocyte homing to mucosal sites. Nonetheless, the activated VLA-4 on some lymphocytes may be involved in MAdCAM-1 recognition or promote binding to MAdCAM-1 in other tissues. By contrast, 38-beta 7 and 38-beta 1 transfectants did not differ in their binding capacity for vascular cell adhesion molecule 1 (VCAM-1) or fibronectin and LPAM-1 did not display any preference for interacting with either MAdCAM-1 or VCAM-1. LPAM-1 may therefore contribute significantly to cellular functions previously attributed to VLA-4. Interestingly, functional analysis of the intraepithelial lymphocyte integrin alpha IEL beta 7 which is structurally related to LPAM-1 did not reveal detectable binding activity for MAdCAM-1, VCAM-1, or fibronectin.
Strauch
U G
UG
Institute of Medical Microbiology and Hygiene, Technical University of Munich, FRG.
Lifka
A
A
Gosslar
U
U
Kilshaw
P J
PJ
Clements
J
J
Holzmann
B
B
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D016466:CHO Cells; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D006224:Cricetinae; D005353:Fibronectins / Q000378:metabolism; D007136:Immunoglobulins / Q000378:metabolism; D039641:Integrin beta Chains; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009088:Mucoproteins / Q000378:metabolism; D011233:Precipitin Tests; D016029:Receptors, Very Late Antigen / Q000378:metabolism; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D005353:Fibronectins; D007136:Immunoglobulins; D039641:Integrin beta Chains; D016023:Integrins; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; C071777:integrin alpha4beta7; C091368:integrin beta7