Toxoplasma gondii alters eicosanoid release by human mononuclear phagocytes: role of leukotrienes in interferon gamma-induced antitoxoplasma activity.
Toxoplasma gondii alters eicosanoid release by human mononuclear phagocytes: role of leukotrienes in interferon gamma-induced antitoxoplasma activity.
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DOI：
10.1084/jem.180.5.1637
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发表时间：
1994-11-01
期刊：
影响因子：
--
通讯作者：
Henderson WR Jr
中科院分区：
文献类型：
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作者：
Yong EC;Chi EY;Henderson WR Jr
弓形虫速殖子显着改变人类单核吞噬细胞释放的类二十烷酸的分布。新鲜分离的、贴壁 2 小时的人单核细胞在受到钙离子载体 A23187 刺激或摄入调理后的酵母聚糖颗粒或热灭活后，释放花生四烯酸代谢的环氧合酶（例如血栓素 [TX] B2、前列腺素 [PG] E2）和 5-脂氧合酶（例如白三烯 [LT] B4、LTC4）产物刚地弓形虫。然而，与活弓形虫一起孵育后，正常和慢性肉芽肿病单核细胞仅释放环氧合酶产物TXB2和PGE2，而不能形成LTB4、LTC4或其他5-脂氧合酶产物。与弓形虫一起培养后，培养 5 天的单核细胞失去释放 TXB2 和 PGE2 的能力。弓形虫显着抑制钙离子载体 A23187 诱导的单核细胞源性巨噬细胞释放 LTB4；热灭活的生物体不会影响钙离子载体 A23187 诱导的 LTB4 释放。弓形虫诱导的钙离子载体 A23187 刺激的单核细胞衍生巨噬细胞对 LTB4 释放的抑制可通过单层细胞的干扰素 (IFN)-γ 处理而逆转。通过透射电子显微镜观察到，LTB4 对生物体的细胞膜和细胞质内容物造成广泛损伤。外源性LTB4 (10(-6) M)诱导非IFN-γ处理的单核细胞来源的巨噬细胞对摄入的弓形虫进行细胞内杀伤。单核细胞来源的巨噬细胞中 IFN-γ 诱导的抗弓形虫活性被选择性 5-脂氧合酶抑制剂齐留通抑制，但不被环氧合酶抑制剂吲哚美辛抑制。这些发现表明 5-脂氧合酶花生四烯酸产品在人巨噬细胞 IFN-γ 诱导的抗弓形虫活性中发挥新作用。
Toxoplasma gondii tachyzoites markedly alter the profile of eicosanoids released by human mononuclear phagocytes. Freshly isolated, 2-h adherent human monocytes release both cyclooxygenase (e.g., thromboxane [TX] B2, prostaglandin [PG] E2) and 5-lipoxygenase (e.g., leukotriene [LT] B4, LTC4) products of arachidonic acid metabolism after stimulation by the calcium ionophore A23187 or ingestion of opsonized zymosan particles or heat-killed T. gondii. However, after incubation with viable T. gondii, normal and chronic granulomatous disease monocytes release only the cyclooxygenase products TXB2 and PGE2 and fail to form LTB4, LTC4, or other 5-lipoxygenase products. Monocytes maintained in culture for 5 d lose this capacity to release TXB2 and PGE2 after incubation with T. gondii. T. gondii significantly inhibit calcium ionophore A23187-induced LTB4 release by monocyte-derived macrophages; heat-killed organisms do not affect this calcium ionophore A23187-induced release of LTB4. T. gondii-induced inhibition of LTB4 release by calcium ionophore A23187-stimulated monocyte-derived macrophage is reversed by interferon (IFN)-gamma treatment of the monolayers. LTB4 induced extensive damage to the cellular membranes and cytoplasmic contents of the organisms as observed by transmission electron microscopy. Exogenous LTB4 (10(-6) M) induced intracellular killing of ingested T. gondii by non-IFN-gamma-treated monocyte-derived macrophages. IFN-gamma-induced antitoxoplasma activity in monocyte- derived macrophages was inhibited by the selective 5-lipoxygenase inhibitor zileuton but not by the cyclooxygenase inhibitor indomethacin. These findings suggest a novel role for 5-lipoxygenase arachidonic acid products in human macrophage IFN-gamma-induced antitoxoplasma activity.