Macrophage chemotactic protein-1 and macrophage inflammatory protein-1α induce nitric oxide release and enhance parasite killing in Leishmania infantum-infected human macrophages
Macrophage chemotactic protein-1 and macrophage inflammatory protein-1α induce nitric oxide release and enhance parasite killing in Leishmania infantum-infected human macrophages
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DOI：
10.1007/s102380200017
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发表时间：
2002-11-01
影响因子：
4.6
通讯作者：
Mitolo, V
中科院分区：
文献类型：
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作者：
Brandonisio, O;Panaro, MA;Mitolo, V
趋化因子是一组结构确定的小蛋白质，其充当白细胞的化学引诱剂，并且参与许多不同的生物活性，包括用于抗菌机制的白细胞活化。我们研究了趋化因子单核细胞趋化蛋白（MCP）（-1）和巨噬细胞炎性蛋白（MIP）-1 α对体外感染婴儿利什曼原虫（Zymode MON 1）的人外周血来源的巨噬细胞释放一氧化氮和杀寄生虫能力的影响。在受感染的人巨噬细胞中，与未处理的细胞相比，MCP-1或MIP-1 α处理显著增强了一氧化氮的产生和杀利什曼能力，达到与干扰素-γ诱导的相同水平。加入L-精氨酸一氧化氮途径的竞争性抑制剂L-N（G）单甲基精氨酸（L-NMMA）可显著降低巨噬细胞的一氧化氮释放和杀寄生虫能力。这些数据表明，MCP-1和MIP-1 α介导巨噬细胞激活一氧化氮释放和随后的寄生虫清除，因此可能在遏制利什曼原虫感染中发挥作用。
Chemokines are a group of structurally defined small proteins that act as chemoattractants for leukocytes and are involved in many different biological activities, including leukocyte activation for antimicrobial mechanisms. We studied the effect of the chemokines monocyte chemotactic protein (MCP)(-1) and macrophage inflammatory protein (MIP)-1alpha on nitric oxide release and parasitocidal ability of peripheral blood-derived human macrophages in vitro infected with Leishmania infantum, zymodeme MON1. In infected human macrophages, treatment with MCP-1 or MIP-1alpha significantly enhanced nitric oxide production and leishmanicidal ability, compared with untreated cells, to the same levels induced by interferon-gamma. Both nitric oxide release and parasitocidal ability of macrophages were significantly reduced by addition of L-N(G)monomethylarginine (L-NMMA), which is a competitive inhibitor of the L-arginine nitric oxide pathway. These data suggest that MCP-1 and MIP-1alpha mediate macrophage activation for nitric oxide release and subsequent parasite clearance, and thus may play a role in the containment of Leishmania infection.