Urosepsis is a severe condition often caused by Escherichia coli that spontaneously have ascended the urinary tract to the kidneys causing pyelonephritis and potentially bacteraemia. The number of sepsis cases has been steadily increasing over the last decades, and there are still no specific, molecular supportive therapies for sepsis to supplement antibiotic treatment. P2X₁ receptors are expressed by a number of immune cells including thrombocytes, which presently have been established as an important player in the acute immune response to bacterial infections. P2X₁ receptor-deficient mice have been shown to be relatively protected against urosepsis, with markedly reduced levels of circulating proinflammatory cytokines and intravascular coagulation. However, here we show that continuous intravenous infusion with P2X₁ receptor antagonist markedly accelerates development of a septic response to induced bacteraemia with uropathogenic E. coli. Mice exposed to the P2X₁ receptor antagonists die very early with haematuria, substantially elevated plasma levels of proinflammatory cytokines, massive intravascular coagulation and a concomitant reduction in circulating thrombocytes. Interestingly, infusion of P2X₁ receptor antagonists causes a marked acute reduction in circulating thrombocytes and a higher number of bacteria in the blood. These data support the notion that the number of functional thrombocytes is important for the acute defence against bacteria in the circulation and that the P2X₁ receptor potentially could be essential for this response.

中文翻译：

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P2X1受体阻滞剂可减少循环血细胞的数量，并降低产生血红素溶酶的尿道炎的总体存活率。

尿失禁是由大肠杆菌引起的严重疾病，大肠杆菌自发地将尿道升至肾脏，引起肾盂肾炎和潜在的菌血症。在过去的几十年中，脓毒症的病例数一直在稳定增长，并且仍然没有针对脓毒症的特殊分子支持疗法来补充抗生素治疗。P2X ₁受体由包括血小板在内的许多免疫细胞表达，这些细胞目前已被确定为对细菌感染的急性免疫反应的重要参与者。P2X ₁缺乏受体的小鼠已经显示出相对抗尿道炎的保护，其循环的促炎细胞因子和血管内凝血水平明显降低。但是，在这里我们显示，连续静脉内输注P2X ₁受体拮抗剂可显着加速对尿毒症性大肠杆菌引起的菌血症的败血症反应的发展。暴露于P2X ₁受体拮抗剂的小鼠死于血尿，血浆中促炎性细胞因子水平明显升高，大量血管内凝血以及随之而来的循环性血小板减少。有趣的是，注入P2X ₁受体拮抗剂会导致循环中的血小板明显减少，血液中细菌数量增加。这些数据支持这样的观点，即功能性血小板的数量对于循环中细菌的急性防御至关重要，而P2X ₁受体可能对此反应至关重要。