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) Ibalpha, 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 Ibalpha-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 Ibalpha 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 Ibalpha and to adherent platelets, the latter adhesion being inhibited by pretreatment of the platelets with mocarhagin, a protease that specifically cleaves GP Ibalpha. Finally, immobilized GP Ibalpha 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.
Pubmed ID: 10899906 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
The American Heart Association (AHA) publishes medical scientific statements on various cardiovascular disease and stroke topics. AHA volunteer scientists and healthcare professionals write the papers. The statements are supported by scientific studies published in recognized journals and have a rigorous review and approval process. Scientific statements generally include a review of data available on a specific subject, an evaluation on its relationship to overall cardiovascular disease science, and often an American Heart Association position on the basis of that evaluation. The American Heart Association sponsors accredited scientific conferences and professional development seminars to disseminate new and emerging scientific knowledge and stimulate discussion on future research and the application of knowledge. Keywords: Heart, Cardiovascular, Disease, Stroke, Volunteer, Scientist, Healthcare, Development, Knowledge,
View all literature mentionsCell line THP-1 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentions