Platelet depletion by anti-CD41 (alphaIIb) mAb injection early but not late in the course of disease protects against Plasmodium berghei pathogenesis by altering the levels of pathogenic cytokines.
Platelet depletion by anti-CD41 (alphaIIb) mAb injection early but not late in the course of disease protects against Plasmodium berghei pathogenesis by altering the levels of pathogenic cytokines.
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DOI：
10.1182/blood-2004-06-2206
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发表时间：
2005-03
期刊：
影响因子：
20.3
通讯作者：
H. C. van der Heyde;I. Gramaglia;Guang Sun;C. Woods
中科院分区：
文献类型：
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作者：
H. C. van der Heyde;I. Gramaglia;Guang Sun;C. Woods
越来越多的证据表明，血小板在伯氏疟原虫感染引起的实验性重症疟疾（ESM）的发病机制中起着关键作用。与感染对照组相比，在伯氏疟原虫感染（早期）第1天注射抗CD41或抗CD61单克隆抗体（mAb）的小鼠从ESM中的存活率显著增加（P <0.001），表明血小板在疾病早期发挥功能。相反，在第4、5和6天（晚期）用抗CD41 mAb处理的小鼠组显示出与对照组相似的死亡率。由于抗CD41单抗在感染第4天的血小板耗竭并不能保护小鼠，而血小板粘附发生在第6天，因此血小板粘附于内皮并不需要介导疟疾发病机制。在疟疾的过程中，在血液中检测到很少的血小板微粒，但检测到大量的红细胞囊泡，微粒和碎片。早期抗CD41 mAb治疗的保护作用与血小板、血小板微粒、红细胞-血小板结合物和红细胞囊泡的数量无关。早期用抗CD41 mAb治疗的小鼠在伯氏疟原虫感染第4天表现出显著改变的细胞因子产生（白细胞介素10 [IL-10]、IL-1 α、IL-6、干扰素-γ [IFN-γ]和肿瘤坏死因子-α [TNF-α]增加;降低IL-2），但与大鼠免疫球蛋白G（IgG）处理的对照组相比，凝血因子没有下降，表明血小板调节致病性细胞因子的水平。
Accumulating evidence indicates that platelets play a critical role in the pathogenesis of experimental severe malaria (ESM) elicited by infection with Plasmodium berghei. Mice injected on day 1 of P berghei infection (early) with either anti-CD41 or anti-CD61 monoclonal antibodies (mAbs) exhibited significantly (P<.001) increased survival from ESM compared with infection controls, indicating that platelets function early in the disease. In contrast, groups of mice treated on days 4, 5, and 6 (late) with anti-CD41 mAb exhibited similar mortality as controls. Because platelet depletion by anti-CD41 mAb on day 4 of infection did not protect mice, and platelet adherence occurs on day 6, platelet adherence to endothelium is not required to mediate malarial pathogenesis. Few platelet microparticles were detected in the blood during the course of malaria, but large numbers of erythrocyte vesicles, microparticles, and debris were detected. The protective effect of early anti-CD41 mAb treatment was independent of the number of platelets, platelet microparticles, erythrocyte-platelet conjugates, and erythrocyte vesicles. Mice treated early with anti-CD41 mAb exhibited markedly altered cytokine production on day 4 of P berghei infection (increased interleukin 10 [IL-10], IL-1alpha, IL-6, interferon-gamma [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]; decreased IL-2) but no decline in coagulation factors compared with rat immunoglobulin G (IgG)-treated controls, indicating that platelets regulate the levels of pathogenic cytokines.