HUMAN MUCOSAL ADDRESSIN CELL-ADHESION MOLECULE-1 (MADCAM-1) DEMONSTRATES STRUCTURAL AND FUNCTIONAL SIMILARITIES TO THE ALPHA(4)BETA(7)-INTEGRIN BINDING DOMAINS OF MURINE MADCAM-1, BUT EXTREME DIVERGENCE OF MUCIN-LIKE SEQUENCES

The mucosal vascular addressin, mucosal addressin cell adhesion molecu le-1 (MAdCAM-1), is an Ig family adhesion receptor preferentially expr essed by venular endothelial cells at sites of lymphocyte extravasatio n in murine mucosal lymphoid tissues and lamina propria, MAdCAM-1 spec ifically binds both human and mouse lymphocytes that express the homin g receptor for Peyer's patches, the integrin alpha(4) beta(7). Functio nal expression cloning was used to isolate a cDNA from a macaque mesen teric lymph node library that encodes the homologue to murine MAdCAM-1 , The macaque cDNA was subsequently used to clone the human homologue as well. Expression of human MAdCAM-1 RNA is restricted to mucosal tis sues, gut-associated lymphoid tissues and spleen, Human MAdCAM-1 selec tively binds both murine and human lymphocyte cell lines expressing al pha(4) beta(7). Human and macaque MAdCAM-1 have two Ig-like domains th at are similar to the two amino-terminal integrin binding domains of m urine MAdCAM-1, The conservation of sequences within the region homolo gous to the mucin/IgA domain of murine MAdCAM-1 is, however, much less apparent. These receptors exhibit considerable variation from murine MAdCAM-1 with respect to the length of the mucin-like sequence and the lack of a membrane proximal Ig (IgA-like) domain. The isolation of th ese different species of MAdCAM-1 demonstrates greater selective press ure for maintenance of amino acids involved in alpha(4) beta(7) bindin g than those sequences presumably involved in the presentation of carb ohydrates for selectin binding.