LPS induces pulmonary intravascular macrophages producing inflammatory mediators via activating NF-κB
LPS induces pulmonary intravascular macrophages producing inflammatory mediators via activating NF-κB
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DOI：
10.1002/jcb.10590
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发表时间：
2003-08-15
影响因子：
4
通讯作者：
Zhu, B
中科院分区：
文献类型：
--
作者：
Chen, ZT;Li, SL;Zhu, B
肺血管内巨噬细胞（PIM）通常负责清除血液传播的病原体，包括内毒素、革兰氏阴性菌的脂多糖。内毒素诱导的急性肺损伤的发病机制中，PIM起着关键作用，这是公认的。然而，PIM参与脂多糖诱导的炎症反应的机制仍不清楚。结果表明：（1）在脂多糖（10 μ g/ml）刺激下，PIM细胞明显增大，细胞间粘附斑变长，伪足内可见颗粒物。(2)脂多糖可上调PIM中TNF-α、IL-1 β、IL-6、IL-8和考克斯-2等炎症介质的表达，这些炎症介质的表达上调与NF-κ B的活化相关。(3)地塞米松和乙酰水杨酸降低了脂多糖刺激的PIM中TNF-α的表达，TNF-α表达的降低也与NF-κ B活化的降低一致。我们的研究结果表明，NF-κ B激活后，吞噬脂多糖导致TNF-α，IL-1 β，IL-6，IL-8和考克斯-2的上调，地塞米松可以减轻。(C)2003 Wiley-Liss，Inc.
Pulmonary intravascular macrophages (PIMs) are often responsible for the clearance of blood-borne pathogens, including endotoxin, lipopolysaccharide of Gram-negative bacteria. It is well accepted that PIMs play a pivotal role in the pathogenesis of endotoxin-induced acute lung injury. However, the mechanisms by which PIMs are involved in the lipopolysaccharide-induced inflammatory responses remain unclear. Through the present study the following results were found: (1) When challenged with lipopolysaccharide (10 mug/ml), PIMs underwent marked cellular enlargement, intercellular adhesion plaques became longer, and some particulates were enwrapped in the pseudopods. (2) Lipopolysaccharide could up-regulate the expression of some inflammatory mediators in PIMs, including TNF-alpha, IL-1beta, IL-6, IL-8, and COX-2, and these up-regulated expression of inflammatory mediators correlated with NF-kappaB activation. (3) Dexamethasone as well as acetylsalicylic acid reduced the expression of TNF-alpha in lipopolysaccharide-challenged PIMs, and the decreased expression of TNF-alpha was also consistent with decreased NF-kappaB activation. Our results suggest that NF-kappaB activation in PIMs followed by phagocytizing lipopolysaccharicle resulted in the up-regulation of TNF-alpha, IL-1beta IL-6, IL-8, and COX-2, which could be alleviated by dexamethasone. (C) 2003 Wiley-Liss, Inc.