THE LEUKOCYTE INTEGRIN MAC-1 (CD11B CD18) CONTRIBUTES TO BINDING OF HUMAN GRANULOCYTES TO COLLAGEN/

Adhesion of polymorphonuclear granulocytes (PMN) to extracellular matr ix proteins has been shown to be important for their migration in vitr o and is thought to participate in PMN recruitment to sites of inflamm ation. Isolated human PMN stimulated with PMA were found to adhere bes t to microtiter wells coated with the novel ECM glycoprotein undulin ( 27 +/- 3% of PMNs added), followed by fibrinogen (25 +/- 2%), collagen type VI (18 +/- 2%), fibronectin (16 +/- 2%), and laminin (15 +/- 3%) . PMN adhesion to other collagens ranged between 3 and 11%. Monoclonal antibodies recognizing CD18 and CD11b subunits of Mac-1 inhibited adh esion of PMN to collagens by an order of magnitude more effectively th an to all noncollagenous substrates. F(ab')(2) fragments of the anti-C D18 antibody were also able to block adhesion to collagens. Anti-LFA-1 (CD11a) and anti-CD44 antibodies did not significantly reduce adhesio n. PMN adhesion was also inhibited by soluble collagens type II and VI (ID50 approximately 75 mu g/ml). Binding of soluble radiolabeled coll agens type II and VI to PMNs was specific and saturable with apparent dissociation constants of 2.2 and 1.9 nM, respectively, and specific b inding of collagens type II and VI was almost completely inhibited by anti-CD18, but not by control antibodies. These data indicate that Mac -1 function is required for binding of human PMN to collagens. (C) 199 5 Academic Press, Inc.