Spirochete-platelet attachment and thrombocytopenia in murine relapsing fever borreliosis
Spirochete-platelet attachment and thrombocytopenia in murine relapsing fever borreliosis
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DOI：
10.1182/blood-2003-02-0426
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发表时间：
2003-10-15
期刊：
影响因子：
20.3
通讯作者：
Leong, JM
中科院分区：
文献类型：
--
作者：
Alugupalli, KR;Michelson, AD;Leong, JM
血小板减少症是常见的人感染回归热疏螺旋体。我们之前的研究表明，在体外，回归热螺旋体赫氏疏螺旋体与人血小板结合并激活，并且在血小板激活后，螺旋体与血小板的高水平附着是由整合素α (IIb) β介导的(3)，这是一种需要血小板激活才能发挥全部功能的受体。本研究证实，小鼠感染乙肝病毒可导致严重的血小板减少症和血小板加速丢失导致的止血功能缺陷。弥散性血管内凝血、免疫性血小板减少性紫癜或脾隔离在该模型中没有明显作用。相反，在感染小鼠的血液中检测到螺旋体-血小板复合物，这表明细菌附着血小板可能导致血小板清除。与此相一致的是，脾肿大和血小板减少与螺旋体血症在时间上相关，血小板减少的严重程度与螺旋体血症的程度直接相关。血小板和整合素α (IIb) β(3)的激活显然不是细菌-血小板结合或血小板清除所必需的，因为循环中细菌结合的血小板没有被激活，感染β(3)缺陷小鼠和野生型小鼠的血小板结合和血小板减少没有区别。这些发现提示，回归热的血小板减少是β(3)非依赖性细菌附着于循环血小板后血小板清除的结果。(C) 2003年由美国血液病学会出版。
Thrombocytopenia is common in persons infected with relapsing fever Borreliae. We previously showed that the relapsing fever spirochete Borrelia hermsii binds to and activates human platelets in vitro and that, after platelet activation, high-level spirochete-platelet attachment is mediated by integrin alpha(IIb)beta(3), a receptor that requires platelet activation for full function. Here we established that B hermsii infection of the mouse results in severe thrombocytopenia and a functional defect in hemostasis caused by accelerated platelet loss. Disseminated intravascular coagulation, immune thrombocytopenic purpura, or splenic sequestration did not play a discernible role in this model. Instead, spirochete-platelet complexes were detected in the blood of infected mice, suggesting that platelet attachment by bacteria might result in platelet clearance. Consistent with this, splenomegally and thrombocytopenia temporally correlated with spirochetemia, and the severity of thrombocytopenia directly correlated with the degree of spirochetemia. Activation of platelets and integrin alpha(IIb)beta(3) were apparently not required for bacterium-platelet binding or platelet clearance because the bacterium-bound platelets in the circulation were not activated, and platelet binding and thrombocytopenia during infection Of beta(3)-deficient and wild-type mice were indistinguishable. These findings suggest that thrombocytopenia of relapsing fever is the result of platelet clearance after beta(3)-independent bacterial attachment to circulating platelets. (C) 2003 by The American Society of Hematology.