Platelet CD36 mediates interactions with endothelial cell-derived microparticles and contributes to thrombosis in mice.
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.
Ghosh
Arunima
A
Department of Biological, Geological, and Environmental Sciences, Cleveland State University, Cleveland, Ohio, USA.
Li
Wei
W
Febbraio
Maria
M
Espinola
Ricardo G
RG
McCrae
Keith R
KR
Cockrell
Erin
E
Silverstein
Roy L
RL
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010718:Phosphatidylserines / Q000378:metabolism; D015539:Platelet Activation; D010974:Platelet Aggregation; D013927:Thrombosis / Q000378:metabolism*
D015415:Biomarkers; D018955:CD36 Antigens; D007074:Immunoglobulin G; D010718:Phosphatidylserines; D000244:Adenosine Diphosphate