Department of Laboratory Medicine and Pathobiology, Keenan Research Centre, Li Ka-Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, Canada.
Thromb Res. 2010 May;125(5):e177-83. doi: 10.1016/j.thromres.2010.01.009.
Multimerin 1 is a stored platelet and endothelial cell adhesive protein that shows significant conservation. In vitro, multimerin 1 supports platelet adhesion and it also binds to collagen and enhances von Willebrand factor-dependent platelet adhesion to collagen. As selective, multimerin 1 deficient mice have not been generated, we investigated multimerin 1 effects on platelet adhesion using a subpopulation of C57BL/6J mice with tandem deletion of the genes for multimerin 1 and alpha-synuclein, a protein that inhibits alpha-granule release in vitro. We postulated that multimerin 1/alpha-synuclein deficient mice might show impaired platelet adhesive function from multimerin 1 deficiency and increased alpha-granule release from alpha-synuclein deficiency.
Platelet function was assessed by intravital microscopy, after ferric chloride injury, using untreated and human multimerin 1-transfused multimerin 1/alpha-synuclein deficient mice, and by in vitro assays of adhesion, aggregation and thrombin-induced P-selectin release.
Multimerin 1/alpha-synuclein deficient mice showed impaired platelet adhesion and their defective thrombus formation at sites of vessel injury improved with multimerin 1 transfusion. Although multimerin 1/alpha-synuclein deficient platelets showed increased P-selectin release at low thrombin concentrations, they also showed impaired adhesion to collagen, and attenuated aggregation with thrombin, that improved with added multimerin 1.
Our data suggest that multimerin 1 supports platelet adhesive functions and thrombus formation, which will be important to verify by generating and testing selective multimerin 1 deficient mice.
多聚蛋白 1 是一种储存的血小板和内皮细胞黏附蛋白，具有显著的保守性。在体外，多聚蛋白 1 支持血小板黏附，它还与胶原结合，并增强血管性血友病因子依赖性血小板黏附到胶原。由于尚未产生选择性的多聚蛋白 1 缺乏小鼠，我们使用 C57BL/6J 小鼠的亚群研究了多聚蛋白 1 对血小板黏附的影响，这些小鼠串联缺失了多聚蛋白 1 和α-突触核蛋白的基因，α-突触核蛋白在体外抑制α-颗粒释放。我们推测，多聚蛋白 1/α-突触核蛋白缺乏小鼠可能由于多聚蛋白 1 缺乏而表现出血小板黏附功能受损，并且由于α-突触核蛋白缺乏而导致α-颗粒释放增加。
通过未处理和输注人多聚蛋白 1 的多聚蛋白 1/α-突触核蛋白缺乏小鼠，以及通过黏附、聚集和凝血酶诱导的 P-选择素释放的体外测定，通过铁氯化物损伤后的活体显微镜评估血小板功能。
多聚蛋白 1/α-突触核蛋白缺乏小鼠表现出血小板黏附受损，其血管损伤部位血栓形成缺陷可通过多聚蛋白 1 输注得到改善。尽管多聚蛋白 1/α-突触核蛋白缺乏的血小板在低凝血酶浓度下显示出增加的 P-选择素释放，但它们也表现出对胶原的黏附受损，并且对凝血酶的聚集减弱，这可以通过添加多聚蛋白 1 得到改善。
我们的数据表明，多聚蛋白 1 支持血小板黏附功能和血栓形成，这将通过生成和测试选择性多聚蛋白 1 缺乏小鼠来验证。
