Occurrence of matrix metalloproteinases and tissue inhibitors of metalloproteinases in tuberculous pleuritis
Occurrence of matrix metalloproteinases and tissue inhibitors of metalloproteinases in tuberculous pleuritis
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DOI：
10.1054/tube.2000.0276
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发表时间：
2001-01-01
期刊：
影响因子：
3.2
通讯作者：
Schauer, J
中科院分区：
文献类型：
--
作者：
Hoheisel, G;Sack, U;Schauer, J
目的：基质金属蛋白酶（MMP）和金属蛋白酶组织抑制剂（TIMP）已被发现在胸腔积液中的高浓度。由于MMP和TIMP可能在结核性胸膜炎的纤维化中发挥作用，因此我们检测了21例结核性胸膜炎患者胸腔积液和血浆中MMP-1、MMP-2、MMP-3、MMP-8、MMP-9、TIMP-1和TIMP-2的浓度。为了调整总蛋白质含量，计算相应的比率。明胶酶谱法测定MMP-2、MMP-9活性，计算MMP-9/MMP-2比值。结果：肺结核患者胸腔积液中MMP-1、MMP-2、MMP-8和MMP-9的浓度均高于CHF患者，而血浆中MMP-1、MMP-2、MMP-8和MMP-9的浓度在两组间无显著性差异。与TB血浆相比，TB胸膜液中MMP-1、MMP-2、TIMP-1和TIMP-2的浓度更高。MMP-3仅以痕量存在。TB组胸水中MMP-9/总蛋白比值高于CHF组（0.4492 ± 0.1633 vs 0.0364 ± 0.0145，P < 0.005），而TIMP-1比值低于CHF组（139.0 ± 28.7 vs 517.8 ± 183.7，P < 0.0005）。在结核性胸膜炎胸腔积液与结核性胸膜炎血浆中，MMP-1、MMP-2、TIMP-1和TIMP-2的比例分别升高（0.46 +/- 0.10 vs 0.17 +/- 0.02; 25.2 +/- 2.8 vs 4.2 +/- 0.9; 139.0 +/- 28.7 vs 27.8 +/- 8.2; 0.67 +/- 0.13 vs 0.18 +/- 0.04，P均< 0.0005）。明胶酶谱显示结核性渗出液中MMP-2和MMP-9的条带亮度不同，但在CHF渗出液中MMP-9条带几乎不可见。因此，与CHF相比，TB患者的MMP-9/MMP-2渗出比率更高（0.46 +/- 0.15 vs 0.05 +/- 0.04，P < 0.0005）。MMP-1、MMP-2、TIMP-1和TIMP-2的区室化，与CHF相比，MMP-1、MMP-2、MMP-8、TIMP-1和TIMP-2的过剩，而MMP-9在结核性胸膜炎的纤维化反应中起重要作用。(C)2001年哈考特出版社有限公司
Objective: Matrix metalloproteinases (MMP) and tissue inhibitors of metalloproteinases (TIMP) have been found in high concentrations in pleural effusions. Because MMP and TIMP may play a part in the causation of the fibrosis seen in tuberculous (TB) pleuritis their occurrence was examined.Design: Pleural effusion fluid and plasma concentrations of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, TIMP-1 and TIMP-2 were determined by ELISA in 21 patients with TB pleuritis. To adjust for the total protein content, respective ratios were calculated. Activities of MMP-2 and MMP-9 were measured by gelatine zymography and the MMP-9/MMP-2 ratios calculated. Pleural effusions and plasma of 15 patients with congestive heat failure (CHF) and plasma of 15 healthy persons (CON) served as controls.Results: Immunoreactive pleural fluid concentrations of MMP-1, MMP-2, MMP-8, and MMP-9 were higher in TB compared to CHF, but plasma concentrations were not different between the groups. TB pleural fluid concentrations of MMP-1, MMP-2, TlMP-1, and TIMP-2 were higher compared to TB plasma. MMP-3 was found in trace amounts only. The MMP-9/total protein ratios in pleural fluid were higher in TB compared to CHF (0.4492 +/- 0.1633 vs 0.0364 +/- 0.0145, P < 0.005) but the TIMP-1 ratios were lower (139.0 +/- 28.7 vs 517.8 +/- 183.7, P < 0.0005). In TB pleural fluid vs TB plasma, the respective MMP-1, MMP-2, TIMP-1, and TIMP-2 ratios were increased (0.46 +/- 0.10 vs 0.17 +/- 0.02; 25.2 +/- 2.8 vs 4.2 +/- 0.9; 139.0 +/- 28.7 vs 27.8 +/- 8.2; 0.67 +/- 0.13 vs 0.18 +/- 0.04, P < 0.0005 each). Gelatine zymography demonstrated MMP-2 and MMP-9 bands of different brightness in TB effusions but in CHF effusions the MMP-9 band was barely visible. The MMP-9/MMP-2 effusion ratios were therefore higher in TB compared to CHF (0.46 +/- 0.15 vs 0.05 +/- 0.04, P < 0.0005).Conclusion: Compartmentalized MMP-1, MMP-2, TIMP-1, and TIMP-2 and, compared to CHF, a surplus of MMP-1, MMP-2, MMP-8, and MMP-9 in the pleural space obviously contribute to the fibrotic reactions in TB pleuritis. (C) 2001 Harcourt Publishers Ltd.