TRAP-positive osteoclast precursors mediate ROS/NO-dependent bactericidal activity via TLR4.
TRAP-positive osteoclast precursors mediate ROS/NO-dependent bactericidal activity via TLR4.
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DOI：
10.1016/j.freeradbiomed.2016.06.021
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发表时间：
2016-08
影响因子：
7.4
通讯作者：
Kawai T
中科院分区：
文献类型：
--
作者：
Nishimura K;Shindo S;Movila A;Kayal R;Abdullah A;Savitri IJ;Ikeda A;Yamaguchi T;Howait M;Al-Dharrab A;Mira A;Han X;Kawai T
用RANKL刺激小鼠单核细胞诱导破骨细胞生成，以检测破骨细胞前体(OCP)和成熟破骨细胞(OCM)可能的杀菌功能与其产生NO和ROS的关系。抗酒石酸酸性磷酸酶(TRAP)阳性的OCP，但很少或没有OCM，吞噬和杀死大肠杆菌与产生活性氧簇(ROS)和一氧化氮(NO)有关。Toll样受体(TLR)-4KO小鼠的TRAP+OCP对大肠杆菌的吞噬作用、ROS和NO的产生显著低于野生型(WT)和TLR2-KO小鼠。有趣的是，来自野生型和TLR2-KO小鼠的TRAP+OCP在吞噬后不能分化为OCM，即使连续暴露于RANKL也是如此。相反，TLR4-KO小鼠的大肠杆菌吞噬的TRAP+OCP可分化为OCM。重要的是，TRAP+OCP产生的NO和ROS似乎都不参与吞噬诱导的破骨细胞生成抑制。这些结果表明，TLR4信号不仅诱导ROS和NO的产生来杀灭吞噬细菌，而且还阻断了OCM的分化。因此，可以得出结论，TRAP+OCP，而不是OCM，可以通过吞噬伴随ROS和NO的产生而介导杀菌活性，而TLR4通过与TLR4相关的重编程向吞噬细胞型转变。
Osteoclastogenesis was induced by RANKL stimulation in mouse monocytes to examine the possible bactericidal function of osteoclast precursors (OCp) and mature osteoclasts (OCm) relative to their production of NO and ROS. Tartrate-resistant acid phosphatase (TRAP)-positive OCp, but few or no OCm, phagocytized and killed Escherichia coli in association with the production of reactive oxygen species (ROS) and nitric oxide (NO). Phagocytosis of E. coli and production of ROS and NO were significantly lower in TRAP+ OCp derived from Toll-like receptor (TLR)-4 KO mice than that derived from wild-type (WT) or TLR2-KO mice. Interestingly, after phagocytosis, TRAP+ OCp derived from wild-type and TLR2-KO mice did not differentiate into OCm, even with continuous exposure to RANKL. In contrast, E. coli-phagocytized TRAP+ OCp from TLR4-KO mice could differentiate into OCm. Importantly, neither NO nor ROS produced by TRAP+ OCp appeared to be engaged in phagocytosis-induced suppression of osteoclastogenesis. These results suggested that TLR4 signaling not only induces ROS and NO production to kill phagocytized bacteria, but also interrupts OCm differentiation. Thus, it can be concluded that TRAP+ OCp, but not OCm, can mediate bactericidal activity via phagocytosis accompanied by the production of ROS and NO via TLR4-associated reprograming toward phagocytic cell type.
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影响因子：
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