Department of Infectious Diseases and Pathobiology, Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland.
Division of Veterinary Anatomy, Vetsuisse Faculty, University of Bern, 3012 Bern; Switzerland.
Toxins (Basel). 2017 Oct 24;9(10):336. doi: 10.3390/toxins9100336.
-toxin (CPB) is the major virulence factor of type C causing a hemorrhagic enteritis in animals and humans. In experimentally infected pigs, endothelial binding of CPB was shown to be associated with early vascular lesions and hemorrhage but without obvious thrombosis of affected vessels, suggesting altered hemostasis in the early phase of the disease. The objective of the present study was to investigate the effect of CPB on platelets, with respect to primary hemostasis. Our results demonstrate that CPB binds to porcine and human platelets and forms oligomers resulting in a time- and dose-dependent cell death. Platelets showed rapid ultrastructural changes, significantly decreased aggregation and could no longer be activated by thrombin. This indicates that CPB affects the physiological function of platelets and counteracts primary hemostasis. Our results add platelets to the list of target cells of CPB and extend the current hypothesis of its role in the pathogenesis of type C enteritis.
细胞毒素(CPB)是 C 型肝炎的主要毒力因子,可导致动物和人类出血性肠炎。在实验感染的猪中,CPB 与内皮细胞的结合与早期血管病变和出血有关,但受影响的血管没有明显的血栓形成,表明疾病早期的止血功能发生改变。本研究的目的是研究 CPB 对血小板的影响,以了解其对初期止血的作用。我们的结果表明,CPB 与猪和人血小板结合并形成寡聚物,导致细胞死亡呈时间和剂量依赖性。血小板显示出快速的超微结构变化,明显减少聚集,并且不能再被凝血酶激活。这表明 CPB 影响血小板的生理功能并拮抗初期止血。我们的研究结果将血小板纳入 CPB 的靶细胞列表,并扩展了其在 C 型肝炎肠炎发病机制中的作用的现有假说。