Carbon monoxide increases macrophage bacterialclearance through toll-like receptor (TLR)4 expression
Carbon monoxide increases macrophage bacterialclearance through toll-like receptor (TLR)4 expression
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DOI：
10.1170/t647
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发表时间：
2005-01-01
影响因子：
1.6
通讯作者：
Chin, BY
中科院分区：
文献类型：
--
作者：
Otterbein, LE;May, A;Chin, BY
一氧化碳（CO）是血红素降解的分解代谢产物，是一种有效的细胞保护剂和强效抗炎分子。一氧化碳的重要细胞靶点之一是巨噬细胞，它是炎症的关键调节因子。在这项研究中，我们研究了CO对培养的巨噬细胞吞噬大肠杆菌能力的影响。暴露于CO可增强大肠杆菌的吞噬作用，但对惰性颗粒物的内化没有影响。CO增加细菌摄取的能力部分是由细胞表面Toll样受体4（TLR4）的重新分布和表达增加所介导的。此外，抑制p38丝裂原活化蛋白激酶（MAPK）可减弱CO/大肠杆菌诱导的TLR4表面表达，并消除CO对大肠杆菌吞噬作用的影响。这些数据共同表明，CO通过p38介导的TLR4表面表达提高大肠杆菌的吞噬速率，并提示CO可能是一种增加细菌清除的潜在治疗方式。
Carbon monoxide (CO), a catabolic product of heme degradation, is an efficacious cytoprotectant and potent anti-inflammatory molecule. One of the important cellular targets of carbon monoxide is the macrophage, a key modulator of inflammation. In this study we investigated the effects of CO on the ability of cultured macrophages to phagocytose E. coli. Exposure to CO augmented E. coli phagocytosis but had no effect on inert particulate matter internalization. The ability of CO to increase uptake of the bacteria was in part mediated by the redistribution and increased expression of Toll-like receptor 4 (TLR4) on the cell surface. Furthermore, inhibition of p38 MAPK attenuated CO/E. coli-induced surface expression of TLR4 and abrogated the CO effects on E. coli phagocytosis. Collectively these data show that CO enhances the rate of E. coli phagocytosis via p38-mediated surface expression of TLR4 and suggest that CO may be a potential therapeutic modality by which to increase bacterial clearance.