Platelet Glycoprotein Ibα Is a Counterreceptor for the Leukocyte Integrin Mac-1 (Cd11b/Cd18)
By D. Simon, Zhiping Chen, Hui Xu, Chester Q. Li, Jing-fei Dong, L. McIntire, Christie M. Ballantyne, Li Zhang, M. Furman, M. Berndt and 1 more. Journal of Experimental Medicine, 2000
612 citations recorded by the source corpus.
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.
Subfields: Genetics, Hematology, Immunology and Allergy
View Paper: https://www.semanticscholar.org/paper/b2b68947ee433d52e6b6583ec7cc1566f34dfae6
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Citations in the corpus
- New fundamentals in hemostasis. (2013, background): “For instance, it contributes to platelet rolling on the endothelium via P-selectin (252), and it binds to the neutrophil receptor integrin M 2 (Mac-1), thus controlling platelet-neutrophil interactions (274).”
- Role of platelets and platelet receptors in cancer metastasis (2018, background): “Next to vWf, thrombin [90], P-selectin [91], leukocyte integrin αLβ2 [92], high molecular weight kininogen, and clotting factors XI and XII have been identified as GPIb-IX-V ligands [93–95].”
- Platelets in Inflammation and Atherogenesis (2015, background): “In fact, GPIb–Mac-1 interaction may be an interesting signaling mechanism in the context of platelet–DC crosstalk modulating atheroprogression (114, 115).”