Differential induction of apoptosis and necrosis in monocytes from patients with tuberculosis and healthy control subjects
Differential induction of apoptosis and necrosis in monocytes from patients with tuberculosis and healthy control subjects
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DOI：
10.1086/386369
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发表时间：
2004-06-01
影响因子：
6.4
通讯作者：
Rojas, M
中科院分区：
文献类型：
--
作者：
Gil, DP;León, LG;Rojas, M
背景结核分枝杆菌和纯化蛋白衍生物（PPD）诱导小鼠巨噬细胞凋亡和人单核细胞和肺泡上皮细胞凋亡和坏死。来自支气管肺泡灌洗液的巨噬细胞和来自结核病（TB）患者的肉芽肿呈现两种类型的细胞死亡;然而，TB中细胞死亡类型的意义仍不确定。PPD阳性对照受试者和TB患者的单核细胞暴露于PPD或M。结核细胞凋亡，坏死，肿瘤坏死因子（TNF）-α阳性和白细胞介素（IL）-10阳性细胞的百分比进行了测定。在培养物上清液中测量乳酸脱氢酶、TNF-α和IL-10的水平。通过阻断实验检测TNF-α和IL-10的作用。PPD和M.结核病诱导PPD阳性对照受试者的单核细胞凋亡，而结核病患者的细胞出现凋亡和坏死。PPD阳性对照受试者的细胞主要产生TNF-α，而TB患者的细胞主要产生IL-10。阻断实验表明，TNF-α和IL-10调节响应于M. tuberculosis.Conclusions.结果表明，暴露于分枝杆菌的单核细胞凋亡可能部分解释PPD阳性对照受试者中发现的保护性免疫反应，而坏死可能是活动性TB患者中发生的细菌传播和组织损伤的决定因素。
Background. Mycobacterium tuberculosis and purified protein derivative (PPD) induce apoptosis in murine macrophages and apoptosis and necrosis in human monocytes and alveolar epithelial cells. Macrophages from bronchoalveolar lavages and granulomas from patients with tuberculosis (TB) present both types of cell death; however, the significance of the type of cell death in TB remains uncertain.Methods. Monocytes from PPD-positive control subjects and from patients with TB were exposed to PPD or M. tuberculosis. Apoptosis, necrosis, and the percentage of tumor necrosis factor (TNF)-alpha-positive and interleukin (IL)-10-positive cells were determined cytofluorometrically. Levels of lactate dehydrogenase, TNF-alpha, and IL-10 were measured in culture supernatants. The role of TNF-alpha and IL-10 was tested by blockade experiments.Results. PPD and M. tuberculosis induced apoptosis in monocytes from PPD-positive control subjects, whereas cells from patients with TB presented apoptosis and necrosis. Cells from PPD-positive control subjects produced mainly TNF-alpha, whereas cells from patients with TB produced mainly IL-10. Blockade experiments suggest that TNF-alpha and IL-10 regulate the type of cell death occurring in response to M. tuberculosis.Conclusions. Results suggest that apoptosis of monocytes exposed to mycobacteria may partly explain the protective immune response found in PPD-positive control subjects, whereas necrosis may be determinant of the bacterial dissemination and tissue damage that occur in patients with active TB.