From the Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands (M.J.E.K., S.d.W., R.N.-U., R.v.K., J.M.E.M.C., J.W.M.H.); Department of Vascular Hematology/Angiogenesis (M.T.), Department of Metabolic Research (P.J.V.), and Department of Biopharmaceutics (S.J.A.K.), Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands; Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands (S.J.A.K.); Department of Dentistry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada (M.F.); Center for Molecular and Vascular Biology, Department of Cardiovascular Diseases, University of Leuven, Leuven, Belgium (P.V., M.F.H.); Laboratory of Vascular Hematology/Angiogenesis, Institute for Transfusion Medicine, DRK Blutspendedienst B-W-Hessen, Goethe University and University Hospital Frankfurt, Frankfurt, Germany (M.T.); and Metabolic Research Laboratories, University of Cambridge, Cambridge, United Kingdom (P.J.V.).
Arterioscler Thromb Vasc Biol. 2014 Jun;34(6):1187-92. doi: 10.1161/ATVBAHA.113.302917. Epub 2014 Mar 27.
Platelets abundantly express the membrane receptor CD36 and store its ligand thrombospondin-1 (TSP1) in the α-granules. We investigated whether released TSP1 can support platelet adhesion and thrombus formation via interaction with CD36.
Mouse platelets deficient in CD36 showed reduced adhesion to TSP1 and subsequent phosphatidylserine expression. Deficiency in either CD36 or TSP1 resulted in markedly increased dissolution of thrombi formed on collagen, although thrombus buildup was unchanged. In mesenteric vessels in vivo, deficiency in CD36 prolonged the time to occlusion and enhanced embolization, which was in agreement with earlier observations in TSP1-deficient mice. Thrombi formed using wild-type blood stained positively for secreted TSP1. Releasate from wild-type but not from TSP1-deficient platelets enhanced platelet activation, phosphatidylserine expression, and thrombus formation on collagen. The enhancement was dependent on CD36 because it was without effect on thrombus formation by CD36-deficient platelets.
These results demonstrate an anchoring role of platelet-released TSP1 via CD36 in platelet adhesion and collagen-dependent thrombus stabilization. Thus, the TSP1-CD36 tandem is another platelet ligand-receptor axis contributing to the maintenance of a stable thrombus.
血小板大量表达膜受体 CD36，并将其配体血小板反应蛋白-1（TSP1）储存在α-颗粒中。我们研究了释放的 TSP1 是否可以通过与 CD36 相互作用来支持血小板黏附和血栓形成。
缺乏 CD36 的小鼠血小板对 TSP1 的黏附以及随后的磷脂酰丝氨酸表达减少。CD36 或 TSP1 的缺乏导致胶原上形成的血栓明显溶解增加，尽管血栓形成没有变化。在体内肠系膜血管中，CD36 的缺乏延长了闭塞时间并增强了栓塞，这与 TSP1 缺乏小鼠的早期观察结果一致。用野生型血液形成的血栓对分泌的 TSP1 染色呈阳性。来自野生型但不是 TSP1 缺乏型血小板的释放物增强了血小板的激活、磷脂酰丝氨酸表达和胶原上的血栓形成。这种增强依赖于 CD36，因为它对 CD36 缺乏型血小板形成的血栓没有影响。
这些结果表明，血小板释放的 TSP1 通过 CD36 在血小板黏附和胶原依赖性血栓稳定中起锚定作用。因此，TSP1-CD36 串联是另一个有助于稳定血栓形成的血小板配体-受体轴。
