结核分枝杆菌及其成分对巨噬细胞和基质金属蛋白酶释放的影响。
Effect of Mycobacterium tuberculosis and its components on macrophages and the release of matrix metalloproteinases.
作者信息
Chang J C, Wysocki A, Tchou-Wong K M, Moskowitz N, Zhang Y, Rom W N
机构信息
Division of Pulmonary and Critical Care Medicine, New York University Medical Center, NY 10016, USA.
出版信息
Thorax. 1996 Mar;51(3):306-11. doi: 10.1136/thx.51.3.306.
BACKGROUND
Pulmonary tuberculosis is associated with caseating necrosis, parenchymal lung destruction, and cavity formation. It was hypothesised that tuberculous lung destruction is mediated, at least in part, by the participation of matrix metalloproteinases released by mononuclear phagocytes.
METHODS
Cells of the myelomonocytic leukaemia cell line THP-1 were incubated with lipoarabinomannan (LAM), the major antigenic cell wall component, and with Mycobacterium tuberculosis and analysed by Northern blot analysis. Two patients with active cavitary tuberculosis also underwent bronchoalveolar lavage and the cells were analysed by Northern blotting.
RESULTS
Incubation of THP-1 cells with LAM resulted in the stimulated release of matrix metalloproteinase-9 (MMP-9), a 92 kDa gelatinase, by 24 hours in a dose-dependent fashion. In addition, Northern analysis revealed that LAM upregulated the gene for MMP-9 by 24 hours, but not the gene for the 72 kDa gelatinase MMP-2. Heat killed M tuberculosis H37Ra also upregulated the MMP-9 gene. Bronchoalveolar lavage of the two patients with active cavitary tuberculosis showed striking upregulation of the MMP-9 gene compared with a normal control using Northern analysis. LAM also upregulated the type I interstitial collagenase (MMP-1) gene by 24 hours in both THP-1 cells and peripheral blood monocytes.
CONCLUSIONS
These data suggest that M tuberculosis and its major cell antigenic component, LAM, stimulate the release of MMP-9 and upregulate the expression of genes for MMP-1 and MMP-9. It is possible that M tuberculosis and its components contribute directly to cavity formation by their ability to stimulate macrophages to release matrix metallo-proteinases that digest collagens I-IV, and indirectly by stimulating the release of the cytokines interleukin 1 beta and tumour necrosis factor alpha that induce fibroblasts to amplify the release of matrix metalloproteinases.
背景
肺结核与干酪样坏死、肺实质破坏及空洞形成有关。据推测，结核性肺破坏至少部分是由单核吞噬细胞释放的基质金属蛋白酶参与介导的。
方法
将髓单核细胞白血病细胞系THP-1细胞与主要抗原性细胞壁成分脂阿拉伯甘露聚糖（LAM）以及结核分枝杆菌一起孵育，并用Northern印迹分析进行检测。两名活动性空洞型肺结核患者也接受了支气管肺泡灌洗，并对细胞进行Northern印迹分析。
结果
THP-1细胞与LAM孵育24小时后，以剂量依赖方式刺激释放基质金属蛋白酶-9（MMP-9，一种92 kDa的明胶酶）。此外，Northern分析显示，LAM在24小时时上调了MMP-9基因，但未上调72 kDa明胶酶MMP-2的基因。热灭活的结核分枝杆菌H37Ra也上调了MMP-9基因。对两名活动性空洞型肺结核患者进行支气管肺泡灌洗，与正常对照相比，Northern分析显示MMP-9基因有显著上调。LAM在THP-1细胞和外周血单核细胞中也在24小时时上调了I型间质胶原酶（MMP-1）基因。
结论
这些数据表明，结核分枝杆菌及其主要细胞抗原成分LAM刺激MMP-9的释放，并上调MMP-1和MMP-9基因的表达。结核分枝杆菌及其成分可能通过刺激巨噬细胞释放消化I-IV型胶原的基质金属蛋白酶直接导致空洞形成，也可能通过刺激细胞因子白细胞介素1β和肿瘤坏死因子α的释放间接导致空洞形成，这些细胞因子可诱导成纤维细胞增加基质金属蛋白酶的释放。
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