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 beta1 or beta7 subunits allowing for a functional comparison of lymphocyte Peyer's patch HEV adhesion molecule 1 (LPAM-1) (alpha4beta7) and very late antigen 4 (VLA-4) (alpha4beta1) in an identical cellular environment. Whereas 38-beta7 transfectants bound to purified and cellular mucosal addressin cell adhesion molecule (MAdCAM-1), unstimulated 38-beta1 cells failed to bind MAdCAM-1. Treatment of 38-beta1 cells with Mn2+ but not with PMA induced low level binding to MAdCAM-1. MAdCAM-1 adhesion of 38-beta7 cells was constitutive and not enhanced by Mn2+ treatment. Similarly, MAdCAM-1-dependent adhesion to mucosal high endothelial venules was shown for 38-beta7 but not for 38-beta1 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-beta7 and 38-beta1 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 alphaIELbeta7 which is structurally related to LPAM-1 did not reveal detectable binding activity for MAdCAM-1, VCAM-1, or fibronectin.