LPS induces pulmonary intravascular macrophages producing inflammatory mediators via activating NF-kappaB.
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 micrograms/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 lipopolysaccharide resulted in the up-regulation of TNF-alpha, IL-1beta, IL-6, IL-8, and COX-2, which could be alleviated by dexamethasone.
Chen
Zheng-Tang
ZT
Cancer Center of People's Liberation Army, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People's Republic of China.
Li
Sheng-Liang
SL
Cai
En-Qi
EQ
Wu
Wei-Ling
WL
Jin
Jing-Sheng
JS
Zhu
Bo
B
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply / Q000166:cytology*; D008262:Macrophage Activation / Q000187:drug effects; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D015854:Up-Regulation / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D003907:Dexamethasone; D001241:Aspirin