Faculty Collaboration Database

Platelet CD36 mediates interactions with endothelial cell-derived microparticles and contributes to thrombosis in mice. J Clin Invest 2008 May;118(5):1934-43

Date

04/24/2008

Pubmed ID

18431509

Pubmed Central ID

PMC2323190

DOI

10.1172/JCI34904

Scopus ID

2-s2.0-43049090815 (requires institutional sign-in at Scopus site)   143 Citations

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 FeCl(3)-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 alpha(2b)beta(3) 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.

Author List

Ghosh A, Li W, Febbraio M, Espinola RG, McCrae KR, Cockrell E, Silverstein RL

Author

Roy L. Silverstein MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenosine Diphosphate
Animals
Biomarkers
Blood Platelets
CD36 Antigens
Cell Membrane
Endothelial Cells
Humans
Immunoglobulin G
Mice
Mice, Inbred C57BL
Mice, Knockout
Phosphatidylserines
Platelet Activation
Platelet Aggregation
Thrombosis