Original Article

Platelet Glycoprotein Ib Is a Counterreceptor for the Leukocyte Integrin Mac-1 (CD11b/CD18)

Correspondence to: Daniel I. Simon, Brigham and Women's Hospital, Cardiovascular Division, 75 Francis St. Tower 3, Boston, MA 02115. Tel:617-732-7820 Fax:617-732-5132 E-mail:dsimon{at}rics.bwh.harvard.edu.

The firm adhesion and transplatelet migration of leukocytes on vascular thrombus 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, a component of the GP Ib-IX-V complex, the platelet von Willebrand factor (vWf) receptor. THP-1 monocytic cells and transfected cells that express Mac-1 adhered to GP Ib–coated wells. Inhibition studies with monoclonal antibodies or receptor ligands showed that the interaction involves the Mac-1 I domain (homologous to the vWf A1 domain), and the GP Ib leucine-rich repeat and COOH-terminal flanking regions. The specificity of the interaction was confirmed by the finding that neutrophils from wild-type mice, but not from Mac-1–deficient mice, bound to purified GP Ib and to adherent platelets, the latter adhesion being inhibited by pretreatment of the platelets with mocarhagin, a protease that specifically cleaves GP Ib. Finally, immobilized GP Ib supported the rolling and firm adhesion of THP-1 cells under conditions of flow. These observations provide a molecular target for disrupting leukocyte–platelet complexes that promote vascular inflammation in thrombosis, atherosclerosis, and angioplasty-related restenosis.

Key Words: inflammation, leukocytes, platelets, adhesion, receptors

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