Grupo de Inmunología Celular e Inmunogenética, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Cell Immunol. 2010;264(1):61-70. doi: 10.1016/j.cellimm.2010.04.012. Epub 2010 May 5.
AA-induced cell death mechanisms acting on human monocytes and monocyte-derived macrophages (MDM), U937 promonocytes and PMA-differentiated U937 cells were studied. Arachidonic acid induced apoptosis and necrosis in monocytes and U937 cells but only apoptosis in MDM and U937D cells. AA increased both types of death in Mycobacterium tuberculosis-infected cells and increased the percentage of TNFalpha+ cells and reduced IL-10+ cells. Experiments blocking these cytokines indicated that AA-mediated death was TNFalpha- and IL-10-independent. The differences in AA-mediated cell death could be explained by high ROS, calpain and sPLA-2 production and activity in monocytes. Blocking sPLA-2 in monocytes and treatment with antioxidants favored M. tuberculosis control whereas AA enhanced M. tuberculosis growth in MDM. Such evidence suggested that AA-modulated effector mechanisms depend on mononuclear phagocytes' differentiation stage.
研究了花生四烯酸（AA）对人单核细胞和单核细胞衍生的巨噬细胞（MDM）、U937 前体细胞和 PMA 分化的 U937 细胞的作用机制。AA 诱导单核细胞和 U937 细胞发生凋亡和坏死，但仅诱导 MDM 和 U937D 细胞发生凋亡。AA 增加了结核分枝杆菌感染细胞的这两种死亡类型，并增加了 TNFalpha+细胞的百分比，减少了 IL-10+细胞。阻断这些细胞因子的实验表明，AA 介导的死亡与 TNFalpha 和 IL-10 无关。AA 介导的细胞死亡的差异可以用单核细胞中高 ROS、钙蛋白酶和 sPLA-2 的产生和活性来解释。在单核细胞中阻断 sPLA-2 并进行抗氧化剂治疗有利于结核分枝杆菌的控制，而 AA 则增强了 MDM 中的结核分枝杆菌生长。这些证据表明，AA 调节的效应机制取决于单核吞噬细胞的分化阶段。
