Differential subcellular localization of COX-2 in macrophages phagocytosing heat-killed Mycobacterium bovis BCG.
Differential subcellular localization of COX-2 in macrophages phagocytosing heat-killed Mycobacterium bovis BCG.
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COX-2 在吞噬热灭活牛分枝杆菌 BCG 的巨噬细胞中的差异亚细胞定位。
DOI：
10.1152/ajpcell.00346.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Shibata,Yoshimi
中科院分区：
文献类型：
--
作者：
Yamashita,Makiko;Tsuji,Shoutaro;Nishiyama,Akihito;Myrvik,QuentinN;Henriksen,RuthAnn;Shibata,Yoshimi
巨噬细胞通过环氧化酶-2（考克斯-2）介导的前列腺素E2（PGE 2）生物合成下调针对细胞内细菌的先天性和获得性免疫应答中的杀微生物活性。先前在小鼠中的研究表明，腹腔内给予热灭活的牛分枝杆菌卡介苗（HK-BCG）导致在7-14天内诱导脾脏释放PGE 2的巨噬细胞。相比之下，HK-BCG在1天内在巨噬细胞中以相对高的水平诱导无催化活性的考克斯-2。在本研究中，我们发现考克斯-2定位于核被膜（NE）的7和14天后，HK-BCG治疗，而考克斯-2是从NE解离治疗后1天。在治疗后1天，大多数考克斯-2阳性巨噬细胞已吞噬HK-BCG。相反，在考克斯-2阳性巨噬细胞中，在处理后7天和14天未检测到细胞内HK-BCG，其中考克斯-2与NE相关。而在体外巨噬细胞吞噬HK-BCG时，所有考克斯-2均与NE相关。因此，HK-BCG的施用诱导脾巨噬细胞中NE解离的催化失活形式或NE相关的催化活性形式的双相考克斯-2表达。无催化活性的考克斯-2阳性巨噬细胞由于缺乏PGE 2生物合成而有效地发挥杀微生物活性。
Cyclooxygenase-2 (COX-2)-mediated prostaglandin E2(PGE2) biosynthesis by macrophages downregulates microbicidal activities in innate and acquired immune responses against intracellular bacteria. Previous studies in mice showed that intraperitoneal administration of heat-killedMycobacterium bovisbacillus Calmette-Guérin (HK-BCG) resulted in induction of splenic PGE2-releasing macrophages in 7–14 days. In contrast, HK-BCG induced catalytically inactive COX-2 at relatively high levels in the macrophages within 1 day. In the present study, we found that COX-2 was localized subcellularly in the nuclear envelope (NE) 7 and 14 days after HK-BCG treatment, whereas COX-2 was dissociated from the NE 1 day after treatment. At 1 day after treatment, the majority of COX-2-positive macrophages had phagocytosed HK-BCG. In contrast, no intracellular HK-BCG was detected 7 and 14 days after treatment in COX-2-positive macrophages, where COX-2 was associated with the NE. However, when macrophages phagocytosed HK-BCG in vitro, all COX-2 was associated with the NE. Thus the administration of HK-BCG induces the biphasic COX-2 expression of an NE-dissociated catalytically inactive or an NE-associated catalytically active form in splenic macrophages. The catalytically inactive COX-2-positive macrophages develop microbicidal activities effectively, since they lack PGE2biosynthesis.