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Original Article

Platelet Glycoprotein Ib Is a Counterreceptor for the Leukocyte Integrin Mac-1 (Cd11b/Cd18)

^a Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts 02115
^b Thrombosis Research Section, Baylor College of Medicine, Houston, Texas 77030
^c Department of Medicine, Baylor College of Medicine, Houston, Texas 77030
^d Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030
^e Cox Laboratory for Bioengineering, Rice University, Houston, Texas 77251
^f American Red Cross, Holland Laboratory, Rockville, Maryland 20855
^g Center for Platelet Function Studies, Division of Cardiovascular Medicine, University of Massachusetts, Worcester, Massachusetts 01655
^h Baker Medical Research Institute, Prahran, Victoria 3181, Australia
Brigham and Women's Hospital, Cardiovascular Division, 75 Francis St. Tower 3, Boston, MA 02115.617-732-5132617-732-7820

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

© 2000 The Rockefeller University Press

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