Platelet CD36 mediates interactions with endothelial cell–derived microparticles and contributes to thrombosis in mice
Arunima Ghosh, … , Erin Cockrell, Roy L. Silverstein
Arunima Ghosh, … , Erin Cockrell, Roy L. Silverstein
Published April 22, 2008
Citation Information: J Clin Invest. 2008;118(5):1934-1943. https://doi.org/10.1172/JCI34904.
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Research Article Hematology

Platelet CD36 mediates interactions with endothelial cell–derived microparticles and contributes to thrombosis in mice

Abstract

CD36 is a scavenger receptor that binds multiple ligands, including phosphatidyl serine (PS). Although CD36– mice do not have a bleeding diathesis, we show here that they do have significantly prolonged thrombotic occlusion times in response to FeCl3-induced vascular injury. Because cell-derived microparticles (MPs) are generated in response to vascular injury and circulate in patients with prothrombotic diseases, we hypothesized that PS exposed on their surfaces could be an endogenous CD36 ligand that transmits an activating signal to platelets. We found that MPs prepared from human ECs, monocytes, or platelets or isolated from blood of normal subjects bound to platelets. Binding was not observed with platelets from CD36– donors and was inhibited by an anti-CD36 antibody or by blockade of exposed PS by annexin V or anti-PS IgM. Preincubation of platelets with MPs led to CD36-dependent augmentation of platelet activation in response to low doses of ADP, as assessed by measuring α2bβ3 activation, P-selectin expression, and aggregation. Immunofluorescence confocal microscopy of murine carotid thrombi from CD36– mice showed a significant decrement in endothelial antigen accumulation, which suggests that CD36 plays a role in MP recruitment into thrombi. These results provide what we believe to be a novel role for CD36 in thrombosis.

Authors

Arunima Ghosh, Wei Li, Maria Febbraio, Ricardo G. Espinola, Keith R. McCrae, Erin Cockrell, Roy L. Silverstein

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Figure 1

Increased thrombosis times in CD36– mice.

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Increased thrombosis times in CD36– mice. (A) Time to thrombotic occ...
(A) Time to thrombotic occlusion of carotid arteries from CD36– (KO) and matched WT mice was measured after 1-min topical application of 7.5% FeCl3. Platelets were labeled by direct injection of fluorescence dye rhodamine 6G into the jugular vein, thrombi formation in the carotid artery was assessed under intravital microscopy, and blood flow was recorded with transonic flowmeter at the same time. n = 6 per group. (B) Representative images of carotid arteries after injury induced by 7.5% FeCl3. At 14 minutes, the artery from the CD36 WT mice was completely occluded, while the CD36– mice showed small thrombi with persistent blood flow. (C) Blood flow in the carotid arteries of WT and CD36– mice, expressed relative to the value before injury. (D) Time to thrombotic occlusion of mesenteric arterioles and venules was measured after application of FeCl3 as in A. n = 10 per group.