Platelet glycoprotein Ib alpha is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18)

The firm adhesion and transplatelet migration of leukocytes on vascular thr ombus are both dependent on the interaction of the leukocyte integrin, Mac- 1, and a heretofore unknown platelet counterreceptor. Here, we identify the platelet counterreceptor as glycoprotein (GP) Ib alpha, a component of the GP Ib-IX-V complex, the platelet von Willebrand factor (vWf) receptor. THP -1 monocytic cells and transfected cells chat express Mac-1 adhered to GP I b alpha-coated wells. Inhibition studies with monoclonal antibodies or rece ptor ligands showed that the interaction involves the Mac-1 I domain (homol ogous to the vWf A1 domain), and the GP Ib alpha leucine-rich repeat and CO OH-terminal flanking regions. The specificity of the interaction was confir med by the finding that neutrophils from wild-type mice, but not from Mac-1 -deficient mice, bound to purified GP Ib alpha and to adherent platelets, t he latter adhesion being inhibited by pretreatment of the platelets with mo carhagin, a protease that specifically cleaves GP Ib alpha. Finally, immobi lized GP Ib alpha supported the rolling and firm adhesion of THP-1 cells un der conditions of flow. These observations provide a molecular target for d isrupting leukocyte-platelet complexes that promote vascular inflammation i n thrombosis, atherosclerosis, and angioplasty-related restenosis.