Influence of endotoxin-induced acute lung injury on pulmonary innate and adaptive immunity
Abstract:Holub M, Lawrence DA. Influence of endotoxin-induced acute lung injury on pulmonary innate and adaptive immunity. APMIS 2003;111:571–80.
Objective. The aim of our study was to analyze pulmonary innate and adaptive immune responses during endotoxemia-induced acute lung injury (ALI). Experimental design. Female BALB/c mice were challenged by endotoxin given intraperitoneally and followed for 24 h by unrestrained plethysmographic analysis. After this period, the mice were sacrificed by CO2 anesthesia and lung histopathology, pulmonary and serum levels of pro-inflammatory cytokines, numbers of lymphocyte subsets in blood and lung, and lung-derived macrophages (Mφ) were analyzed. Main results. Animals with endotoxemia demonstrated significant depression of tidal volumes indicating respiratory failure compared to control mice. Lung histopathology of endotoxin-exposed animals revealed alveolar leakage characterizing ALI. Pulmonary levels of interleukin (IL)-1β, IL-6 and interferon (IFN)-γ in animals with endotoxemia were significantly elevated, whereas serum levels of IL-6 only were increased. IFN-γ was strongly expressed by lung-derived Mφ with high CD11b expression, and this subset significantly increased in the lungs after endotoxin challenge. Additionally, the numbers of lung-resident CD4+ and total T-lymphocytes were significantly reduced after challenge. Conclusion. These data suggest that endotoxemia-induced ALI is associated with exaggerated and sustained pulmonary innate immune responses partly mediated by activated Mφ, whereas adaptive immunity in the lungs is compromised.