Interleukin-6 Mediates the Platelet Abnormalities and Thrombogenesis Associated with Experimental Colitis
Interleukin-6 Mediates the Platelet Abnormalities and Thrombogenesis Associated with Experimental Colitis
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DOI：
10.1016/j.ajpath.2013.03.014
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发表时间：
2013-07-01
影响因子：
6
通讯作者：
Granger, D. Neil
中科院分区：
文献类型：
--
作者：
Senchenkova, Elena Y.;Komoto, Shunsuke;Granger, D. Neil
临床研究和动物实验表明，结肠炎症与血小板数量和反应性增加、凝血异常和血栓形成增强有关。本研究的目的是确定IL-6对实验性结肠炎期间发生的血小板增多、过度激动剂诱导的血小板聚集和增强的肠外血栓形成的贡献。在患有葡聚糖硫酸钠（DSS）诱导的结肠炎的野生型（WT）和IL-6缺陷（IL-6（-/-））小鼠中测量成熟和未成熟血小板的数量、血小板寿命、凝血酶诱导的血小板聚集反应以及提睾肌小动脉中光/染料诱导的血栓形成。WT小鼠中的DSS结肠炎与血小板增多相关，成熟和未成熟血小板数量增加，血小板寿命无变化。在IL-6（-/-）小鼠中不存在血小板增多反应。DSS治疗还增强了血小板对凝血酶的聚集反应，并加速了WT小鼠的血栓形成，但在IL-6（-/-）小鼠中没有。给予WT小鼠外源性IL-6引起血栓形成的剂量依赖性增强。这些发现表明，IL-6介导的血小板增多，血小板高反应性，并加速血栓的发展与实验性结肠炎。IL-6依赖性结肠炎诱导的血小板增多似乎是由于血小板生成增强，因为血小板寿命不变。
Clinical studies and animal experimentation have shown that colonic inflammation is associated with an increased number and reactivity of platelets, coagulation abnormalities, and enhanced thrombus formation. The objective of this study was to define the contribution of IL-6 to the thrombocytosis, exaggerated agonist-induced platelet aggregation, and enhanced extra-intestinal thrombosis that occur during experimental colitis. The number of mature and immature platelets, platelet life span, thrombin-induced platelet aggregation response, and light/dye-induced thrombus formation in cremaster muscle arterioles were measured in wild-type (WT) and IL-6 deficient (IL-6(-/-)) mice with dextran sodium sulfate (DSS)-induced colitis. DSS colitis in WT mice was associated with thrombocytosis with an elevated number of both mature and immature platelets and no change in platelet life span. The thrombocytosis response was absent in IL-6(-/-) mice. DSS treatment also enhanced the platelet aggregation response to thrombin and accelerated thrombus development in WT mice, but not in IL-6(-/-) mice. Exogenous IL-6 administered to WT mice elicited a dose-dependent enhancement of thrombus formation. These findings indicate that IL-6 mediates the thrombocytosis, platelet hyperreactivity, and accelerated thrombus development associated with experimental colitis. The IL-6 dependent colitis-induced thrombocytosis appears to result from an enhancement of thrombopoiesis because platelet life span is unchanged.