Influence of endotoxin-induced acute lung injury on pulmonary innate and adaptive immunity.
OBJECTIVE
The aim of our study was to analyze pulmonary innate and adaptive immune responses during endotoxemia-induced acute lung injury (ALI).


METHODS
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 (Mphi) were analyzed.


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)-1beta, IL-6 and interferon (IFN)-gamma in animals with endotoxemia were significantly elevated, whereas serum levels of IL-6 only were increased. IFN-gamma was strongly expressed by lung-derived Mphi 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.


CONCLUSIONS
These data suggest that endotoxemia-induced ALI is associated with exaggerated and sustained pulmonary innate immune responses partly mediated by activated Mphi, whereas adaptive immunity in the lungs is compromised.
Holub
Michal
M
Clinical and Experimental Endocrinology and Immunology, Wadsworth Center, Albany, USA. michal.holub@fnb.cz
Lawrence
David A
DA
D000222:Adaptation, Physiological; D000818:Animals; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D019446:Endotoxemia / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004731:Endotoxins / Q000633:toxicity*; D005260:Female; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D055370:Lung Injury; D016131:Lymphocyte Subsets / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013990:Tidal Volume
D016207:Cytokines; D004731:Endotoxins; D018836:Inflammation Mediators; D007371:Interferon-gamma