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.