Polymicrobial sepsis and endotoxemia promote microvascular thrombosis via distinct mechanisms.
Polymicrobial sepsis and endotoxemia promote microvascular thrombosis via distinct mechanisms.
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DOI：
10.1111/j.1538-7836.2010.03853.x
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Rumbaut RE
中科院分区：
文献类型：
--
作者：
Patel KN;Soubra SH;Lam FW;Rodriguez MA;Rumbaut RE
我们最近报道，内毒素血症促进野生型小鼠提睾肌小静脉微血管血栓形成，但在Toll样受体4（TLR 4）或血管性血友病因子（VWF）缺陷的小鼠中没有。确定盲肠结扎/穿孔（CLP）诱导的多微生物脓毒症的临床相关模型是否通过与内毒素血症相同的机制诱导类似的反应。我们在野生型小鼠和Toll样受体-4（C57 BL/10 ScNJ）、Toll样受体-2（TLR-2）或VWF缺陷小鼠的提睾肌微循环中使用了血栓形成的光/染料损伤模型。小鼠接受CLP或假手术，或腹膜内注射内毒素（LPS）或盐水。在CLP模型中，我们评估了补液对血栓反应的影响。CLP和LPS均增强野生型小鼠的血栓闭塞。与LPS相比，CLP增强TLR 4和VWF缺陷菌株的血栓形成。虽然TLR-2缺陷小鼠在CLP后没有表现出增强的血栓形成，但LPS增强了这些小鼠中的血栓形成。LPS，但不是CLP，增加血浆VWF抗原相对于对照组。脓毒症小鼠，特别是那些接受CLP的小鼠，出现了显著的血液浓缩。用等渗盐水静脉补液可防止CLP引起的血液浓缩和血栓前反应，但补液不能防止LPS引起的血栓前反应。由CLP和内毒素血症诱导的多微生物脓毒症通过不同的机制促进微血管血栓形成;由CLP诱导的增强的血栓形成需要TLR-2而不是TLR 4或VWF。静脉补液对多种微生物脓毒症微血管血栓形成的有益作用仍有待研究。
We reported recently that endotoxemia promotes microvascular thrombosis in cremaster venules of wild type mice, but not in mice deficient in toll-like receptor-4 (TLR4) or von Willebrand factor (VWF). To determine whether the clinically relevant model of polymicrobial sepsis induced by cecal ligation/perforation (CLP) induces similar responses via the same mechanisms as endotoxemia. We used a light/dye injury model of thrombosis in the cremaster microcirculation of wild type mice and mice deficient in toll-like receptor-4 (C57BL/10ScNJ), toll-like receptor-2 (TLR-2), or VWF. Mice underwent CLP or sham surgery, or an intraperitoneal injection of endotoxin (LPS) or saline. In the CLP model, we assessed the influence of fluid replacement on thrombotic responses. Both CLP and LPS enhanced thrombotic occlusion in wild type mice. In contrast to LPS, CLP enhanced thrombosis in TLR4- and VWF-deficient strains. While TLR-2-deficient mice did not demonstrate enhanced thrombosis following CLP, LPS enhanced thrombosis in these mice. LPS, but not CLP, increased plasma VWF antigen relative to controls. Septic mice, particularly those undergoing CLP, developed significant hemoconcentration. Intravenous fluid replacement with isotonic saline prevented the hemoconcentration and prothrombotic responses to CLP, though fluids did not prevent the prothrombotic response to LPS. Polymicrobial sepsis induced by CLP and endotoxemia promote microvascular thrombosis via distinct mechanisms; enhanced thrombosis induced by CLP requires TLR-2 but not TLR4 or VWF. The salutary effects of intravenous fluid replacement on microvascular thrombosis in polymicrobial sepsis remain to be characterized.
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DOI：
10.1084/jem.20062354
发表时间：
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期刊：
The Journal of experimental medicine
影响因子：
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作者：
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