Platelet factor 4 mediates inflammation in experimental cerebral malaria.
Platelet factor 4 mediates inflammation in experimental cerebral malaria.
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DOI：
10.1016/j.chom.2008.07.003
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发表时间：
2008-08-14
影响因子：
30.3
通讯作者：
Morrell, Craig N
中科院分区：
文献类型：
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作者：
Srivastava, Kalyan;Cockburn, Ian A;Swaim, AnneMarie;Thompson, Laura E;Tripathi, Abhai;Fletcher, Craig A;Shirk, Erin M;Sun, Henry;Kowalska, M Anna;Fox-Talbot, Karen;Sullivan, David;Zavala, Fidel;Morrell, Craig N
脑型疟疾是儿童恶性疟原虫感染的主要并发症。脑型疟疾的发病机制涉及血管炎症、免疫刺激和脑毛细血管阻塞。血小板在免疫反应和血管阻塞中起重要作用。我们现在证明，血小板衍生的趋化因子，血小板因子4（PF 4）/CXCL 4，促进实验性脑型疟疾的发展。疟原虫感染的红细胞（RBC）激活血小板，不依赖于血管效应，导致血浆PF 4增加。PF 4或CXCR 3缺失小鼠具有较少的ECM，减少的脑T细胞募集，并且血小板耗竭或阿司匹林治疗减少了ECM的发展。我们的结论是，疟原虫感染的红细胞可以激活血小板和血小板衍生的PF 4，然后有助于免疫激活和T细胞运输的ECM的发病机制的一部分。
Cerebral malaria is a major complication of Plasmodium falciparum infection in children. The pathogenesis of cerebral malaria involves vascular inflammation, immune stimulation and obstruction of cerebral capillaries. Platelets have a prominent role in both immune responses and vascular obstruction. We now demonstrate that the platelet derived chemokine, platelet factor 4 (PF4)/CXCL4, promotes the development of experimental cerebral malaria. Plasmodium infected red blood cells (RBC) activated platelets independent of vascular effects, resulting in increased plasma PF4. PF4 or CXCR3 null mice had less ECM, decreased brain T-cell recruitment, and platelet depletion or aspirin treatment reduced the development of ECM. We conclude that Plasmodium infected RBC can activate platelets and platelet derived PF4 then contributes to immune activation and T-cell trafficking as part of the pathogenesis of ECM.