Platelet Glycoprotein Ibα Is a Counterreceptor for the Leukocyte Integrin Mac-1 (Cd11b/Cd18)
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Open Access
- 10 July 2000
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 192 (2), 193-204
- https://doi.org/10.1084/jem.192.2.193
Abstract
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) Ibα, 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 Ibα–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 Ibα 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 Ibα and to adherent platelets, the latter adhesion being inhibited by pretreatment of the platelets with mocarhagin, a protease that specifically cleaves GP Ibα. Finally, immobilized GP Ibα 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.Keywords
This publication has 94 references indexed in Scilit:
- Identification of a Novel Recognition Sequence for Integrin αMβ2 within the γ-chain of FibrinogenPublished by Elsevier BV ,1998
- Unexpected, Discordant Effects of Aspirin on Platelet ReactivityJournal of the American College of Cardiology, 1998
- Identification and Reconstruction of the Binding Site within αMβ2 for a Specific and High Affinity Ligand, NIFPublished by Elsevier BV ,1997
- A Discrete Site Modulates Activation of I DomainsPublished by Elsevier BV ,1996
- A functional integrin ligand on the surface of platelets: intercellular adhesion molecule-2.JCI Insight, 1994
- The dynamic regulation of integrin adhesivenessCurrent Biology, 1994
- Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigmCell, 1994
- Binding of the integrin Mac-1 (CD11b/CD18) to the third immunoglobulin-like domain of ICAM-1 (CD54) and its regulation by glycosylationCell, 1991
- Oligospecificity of the cellular adhesion receptor Mac-1 encompasses an inducible recognition specificity for fibrinogen.The Journal of cell biology, 1988
- Isolation and characterization of the α and β chains of human platelet glycoprotein IbBiochemical and Biophysical Research Communications, 1987