Platelet factor 4 regulation of monocyte KLF4 in experimental cerebral malaria.
Platelet factor 4 regulation of monocyte KLF4 in experimental cerebral malaria.
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DOI：
10.1371/journal.pone.0010413
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发表时间：
2010-05-03
期刊：
影响因子：
3.7
通讯作者：
Morrell CN
中科院分区：
文献类型：
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作者：
Srivastava K;Field DJ;Aggrey A;Yamakuchi M;Morrell CN
脑型疟疾仍然是儿童恶性疟原虫感染的一种难以治疗的并发症。我们已经表明，血小板可以在实验性脑型疟疾（ECM）的主要有害的免疫功能。我们已经确定为特别重要的血小板衍生介质之一是血小板因子4/CXCL 4。我们之前的工作表明，PF 4 −/−小鼠受到ECM的保护，血浆细胞因子减少，T细胞向大脑的运输减少。我们现在表明，PF 4驱动单核细胞细胞因子的生产在Kruppel样因子4（KLF 4）依赖的方式。单核细胞耗竭的伯氏疟原虫感染小鼠的存活率提高，KLF 4在对照组中大大增加，但单核细胞耗竭的小鼠没有增加。PF 4 −/−小鼠大脑单核细胞运输较少，KLF 4表达无变化。这些数据表明，PF 4诱导单核细胞KLF 4表达可能是ECM发病机制中的重要步骤。
Cerebral malaria continues to be a difficult to treat complication of Plasmodium falciparum infection in children. We have shown that platelets can have major deleterious immune functions in experimental cerebral malaria (ECM). One of the platelet derived mediators we have identified as particularly important is platelet factor 4/CXCL4. Our prior work demonstrated that PF4−/− mice are protected from ECM, have reduced plasma cytokines, and have reduced T-cell trafficking to the brain. We now show that PF4 drives monocyte cytokine production in a Kruppel like factor 4 (KLF4) dependent manner. Monocyte depleted Plasmodium berghei infected mice have improved survival, and KLF4 is greatly increased in control, but not monocyte depleted mice. PF4−/− mice have less cerebral monocyte trafficking and no change in KLF4 expression. These data indicate that PF4 induction of monocyte KLF4 expression may be an important step in the pathogenesis of ECM.