Modulation of cytokine profiles by malaria pigment - hemozoin: role of IL-10 in suppression of proliferative repsonses of mitogen stimulated human PBMC
Modulation of cytokine profiles by malaria pigment - hemozoin: role of IL-10 in suppression of proliferative repsonses of mitogen stimulated human PBMC
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DOI：
10.1016/j.cyto.2004.08.002
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发表时间：
2004-12-21
期刊：
影响因子：
3.8
通讯作者：
Shastry, P
中科院分区：
文献类型：
--
作者：
Deshpande, P;Shastry, P
疟原虫色素疟原虫色素（Hz）被循环和驻留吞噬细胞内化并调节它们的功能。我们在这里报告Hz从恶性疟原虫抑制PHA刺激的人外周血单个核细胞（PBMC）的增殖反应，在剂量依赖性的方式。Hz吞噬的单核细胞/巨噬细胞（MO/MQ）分泌高水平的IL-10，IL-1 β和TNF-α，但增殖抑制是由IL-10单独介导的，这是逆转的细胞因子的中和。在Hz负载的MO/MQ细胞存在下刺激的PBMC的上清液中观察到IL-2、IL-12和IFN-γ水平的急剧降低。这些细胞因子的外源性添加没有消除免疫抑制，表明这些细胞因子在IL-10存在下不能增强增殖。我们提供了IL-10水平与MO/MQ中Hz负荷呈正相关的额外数据。IL-10分泌的动力学分析，直到第6天在MO/MQ培养物与Hz喂养显示，高水平的IL-10分泌后摄取的第一个48小时内，并在以后的时间点急剧下降。(C)2004 Elsevier Ltd.保留所有权利。
The malaria parasite pigment hemozoin (Hz) is internalized by circulating and resident phagocytes and modulates their functions. We report here that Hz from Plasmodium falciparum inhibits proliferative responses of PHA stimulated human peripheral blood mononuclear cells (PBMC) in a dose dependent manner. Hz phagocytosed monocyte/macrophages (MO/MQ) secreted high levels of IL-10, IL-1beta and TNF-alpha, but inhibition of proliferation was mediated by IL-10 alone which was reversed by neutralization of the cytokine. Drastic decrease in the levels of IL-2, IL-12 and IFN-gamma were observed in supernatants from PBMC stimulated in the presence of Hz loaded MO/MQ cells. Exogenous addition of these cytokines did not abrogate immunosuppression indicating the inability of these cytokines to enhance proliferation in the presence of IL-10. We provide additional data that the IL-10 levels correlated positively with the load of Hz in the MO/MQ. Kinetics of IL-10 secretion analyzed up to day 6 in MO/MQ cultures fed with Hz revealed that high levels of IL-10 were secreted during the first 48 h after ingestion and decreased drastically at later time points. (C) 2004 Elsevier Ltd. All rights reserved.