Dockrell D H, Lee M, Lynch D H, Read R C
Division of Genomic Medicine, University of Sheffield Medical School, Sheffield S10 2RX, United Kingdom.
J Infect Dis. 2001 Sep 15;184(6):713-22. doi: 10.1086/323084. Epub 2001 Aug 24.
Apoptosis of macrophages may be a pathogen-directed mechanism of immune escape or may represent appropriate host response to infection. Human monocyte-derived macrophages (MDMs) from healthy donors (C-MDMs) exhibited low-level constitutive apoptosis, but culture of MDMs with opsonized serotype I Streptococcus pneumoniae (I-MDMs) for 20 h resulted in significantly increased apoptosis. I-MDM apoptosis was associated with phagocytosis of bacteria and intracellular killing that was blocked by the caspase inhibitor z-VAD-fmk but not by Fas-blocking antibody. Paraformaldehyde-fixed I-MDMs induced apoptosis in uninfected syngeneic monocytes at levels greater than those in monocytes incubated alone or incubated with fixed C-MDMs. Apoptosis of syngeneic monocytes was blocked by anti-Fas antibody. The immune response of macrophages to S. pneumoniae includes a novel form of apoptosis that is associated with successful phagocytosis and bacterial killing. This response in vivo may regulate the inflammatory response to infection during a successful host response against S. pneumoniae.
巨噬细胞凋亡可能是病原体导向的免疫逃逸机制，也可能代表宿主对感染的适当反应。来自健康供体的人单核细胞衍生巨噬细胞（C-MDMs）表现出低水平的组成性凋亡，但用调理的I型肺炎链球菌培养MDMs 20小时（I-MDMs）会导致凋亡显著增加。I-MDM凋亡与细菌吞噬和细胞内杀伤有关，半胱天冬酶抑制剂z-VAD-fmk可阻断这种杀伤，但Fas阻断抗体不能。多聚甲醛固定的I-MDMs诱导未感染的同基因单核细胞凋亡，其水平高于单独培养或与固定的C-MDMs共同培养的单核细胞。同基因单核细胞的凋亡被抗Fas抗体阻断。巨噬细胞对肺炎链球菌的免疫反应包括一种与成功吞噬和细菌杀伤相关的新型凋亡形式。在体内，这种反应可能在宿主对肺炎链球菌的成功反应过程中调节对感染的炎症反应。
