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LPS induces pulmonary intravascular macrophages producing inflammatory mediators via activating NF-kappaB
Zheng-Tang Chen1, Sheng-Liang Li, En-Qi Cai
1Cancer Center of People's Liberation Army, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, People's Republic of China.
Abstract:
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.
Insights
Pulmonary intravascular macrophages (PIMs) engulf lipopolysaccharide, triggering inflammatory responses via NF-kappaB activation. Dexamethasone and aspirin reduce this inflammation, suggesting PIMs are key in endotoxin-induced acute lung injury.
Area of Science:
- Immunology
- Cell Biology
- Pathology
Background:
- Pulmonary intravascular macrophages (PIMs) clear pathogens like lipopolysaccharide (LPS).
- PIMs are implicated in endotoxin-induced acute lung injury.
- Mechanisms of PIMs in LPS-induced inflammation are not fully understood.
Purpose of the Study:
- Investigate PIMs' role in LPS-induced inflammatory responses.
- Elucidate the signaling pathways involved in PIMs' reaction to LPS.
- Evaluate the effects of anti-inflammatory drugs on LPS-challenged PIMs.
Main Methods:
- Challenged PIMs with lipopolysaccharide (10 µg/ml).
- Assessed PIM morphology, intercellular adhesion, and phagocytosis.
- Measured inflammatory mediator expression (TNF-α, IL-1β, IL-6, IL-8, COX-2) and NF-κB activation.
- Treated LPS-challenged PIMs with dexamethasone and acetylsalicylic acid.
Main Results:
- LPS induced PIMs enlargement, adhesion plaque elongation, and phagocytosis.
- LPS upregulated inflammatory mediators (TNF-α, IL-1β, IL-6, IL-8, COX-2) in PIMs, correlating with NF-κB activation.
- Dexamethasone and acetylsalicylic acid reduced TNF-α expression and NF-κB activation in LPS-challenged PIMs.
Conclusions:
- NF-κB activation in PIMs following LPS phagocytosis upregulates key inflammatory mediators.
- This inflammatory cascade contributes to acute lung injury pathogenesis.
- Dexamethasone demonstrates potential in alleviating LPS-induced PIM inflammation.