Persistent inactivation of macrophage cyclooxygenase-2 in mycobacterial pulmonary inflammation.
Persistent inactivation of macrophage cyclooxygenase-2 in mycobacterial pulmonary inflammation.
复制标题
分枝杆菌肺部炎症中巨噬细胞环氧合酶-2 的持续失活。
DOI：
10.1165/rcmb.2008-0230oc
复制
发表时间：
2009
影响因子：
6.4
通讯作者：
Shibata,Yoshimi
中科院分区：
文献类型：
--
作者：
Shinohara,Tsutomu;Pantuso,Traci;Shinohara,Shizuka;Kogiso,Mari;Myrvik,QuentinN;Henriksen,RuthAnn;Shibata,Yoshimi
在组织巨噬细胞（M β）中诱导环氧合酶-2（考克斯-2）增加前列腺素E2（PGE 2）的释放，可能下调肉芽肿性炎症。在分枝杆菌的作用下，局部巨噬细胞表达核被膜（NE）相关或NE解离的考克斯-2。持续性分枝杆菌肺部炎症的特征是肺泡巨噬细胞表达NE-解离的（无活性的）考克斯-2而不释放PGE 2。在本研究中，我们检测了鼻内暴露于热灭活牛分枝杆菌卡介苗（HK-BCG）后肺泡M细胞中考克斯-2的表达。给药后用生理盐水灌洗C57 B1/6小鼠全肺，检测肺泡巨噬细胞考克斯-2表达和PGE 2释放，以及肺灌洗液中肿瘤坏死因子（TNF）-α和一氧化氮（NO）水平。Western印迹法检测不到正常肺泡巨噬细胞的考克斯-2水平。然而，鼻内给药后1天，几乎所有的肺泡巨噬细胞都吞噬了HK-BCG，并表达NE-解离的考克斯-2，而PGE 2的释放没有任何增加。在鼻内给药后28天，68%的肺泡巨噬细胞仍然含有BCG和NE-解离形式的考克斯-2。NE相关的（活性）考克斯-2在肺泡巨噬细胞中未观察到。相反，在腹腔注射HK-BCG后7天，不再检测到含有HK-BCG的腹膜M细胞。鼻内给药后28 d，肺灌洗液中TNF-α和亚硝酸盐水平显著高于对照组。我们的研究结果表明，分枝杆菌肺炎与肺泡巨噬细胞产生PGE 2的抑制，以及NE解离的考克斯-2的表达有关。
The induction of cyclooxygenase-2 (COX-2) in tissue macrophages (M∅) increases prostaglandin E2(PGE2) release, potentially down-regulating granulomatous inflammation. In response toMycobacteria, local M∅ express COX-2, which is either nuclear envelope (NE)-associated or NE-dissociated. Persistent mycobacterial pulmonary inflammation is characterized by alveolar M∅ expressing NE-dissociated (inactive) COX-2 without release of PGE2. In this study, we examined COX-2 in alveolar M∅ after intranasal exposure to heat-killedMycobacterium bovisBCG (HK-BCG). After administration, whole lungs of C57Bl/6 mice were lavaged with saline; COX-2 expression and PGE2release by alveolar M∅ and tumor necrosis factor (TNF)-α and nitric oxide levels in the lung lavage were monitored. Normal alveolar M∅ had undetectable levels of COX-2 on Western blots. However, 1 day after intranasal administration, almost all alveolar M∅ had phagocytosed HK-BCG and expressed NE-dissociated COX-2 without any increase in the release of PGE2. At 28 days after intranasal administration, 68% of alveolar M∅ still contained both BCG and the NE-dissociated form of COX-2. NE-associated (active) COX-2 was not observed in alveolar M∅. In contrast, 7 days after intraperitoneal injection of HK-BCG, peritoneal M∅ containing HK-BCG were no longer detected. At 28 days after intranasal administration, TNF-α and nitrite levels in the lung lavage fluid were significantly higher than those in controls. Our results indicate that mycobacterial pulmonary inflammation is associated with suppressed PGE2production by alveolar M∅, with expression of COX-2 dissociated from the NE.