Effect of Mycobacterium tuberculosis and its components on macrophages and the release of matrix metalloproteinases
Effect of Mycobacterium tuberculosis and its components on macrophages and the release of matrix metalloproteinases
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DOI：
10.1136/thx.51.3.306
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发表时间：
1996-03-01
期刊：
影响因子：
10
通讯作者：
Rom, WN
中科院分区：
文献类型：
--
作者：
Chang, JC;Wysocki, A;Rom, WN
背景-肺结核与干酪样坏死、肺实质破坏和空洞形成有关.据推测，结核性肺破坏介导的，至少部分地，由单核吞噬细胞释放的基质金属蛋白酶的参与。方法-骨髓单核细胞白血病细胞系THP-1细胞与脂阿拉伯甘露聚糖（LAM），主要抗原细胞壁成分，结核分枝杆菌和北方印迹分析。两名活动性空洞结核患者也进行了支气管肺泡灌洗和细胞进行了分析，通过北方blotting.Results -温育的THP-1细胞与LAM导致刺激释放基质金属蛋白酶-9（MMP-9），92 kDa明胶酶，由24小时在剂量依赖性的方式。此外，北方分析显示，LAM上调MMP-9的基因24小时，但不是72 kDa明胶酶MMP-2的基因。热灭活结核分枝杆菌H37 Ra也上调MMP-9基因。使用北方分析，与正常对照相比，两名活动性空洞结核患者的支气管肺泡灌洗显示MMP-9基因显著上调。LAM还上调I型间质胶原酶（MMP-1）基因24小时在THF-1细胞和外周血monocytes.Conclusions -这些数据表明，结核分枝杆菌及其主要细胞抗原成分，LAM，刺激释放MMP-9和上调MMP-1和MMP-9的基因表达。结核分枝杆菌及其组分可能通过刺激巨噬细胞释放基质金属蛋白酶（其消化胶原蛋白I-IV）的能力直接促成空洞形成，并通过刺激细胞因子白介素1 β和肿瘤坏死因子α（其诱导成纤维细胞放大基质金属蛋白酶的释放）的释放间接促成空洞形成。
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 THF-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 to cavity directly formation by their ability to stimulate macrophages to release matrix metalloproteinases 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.