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Influence of endotoxin‐induced acute lung injury on pulmonary innate and adaptive immunity
Author(s) -
HOLUB MICHAL,
LAWRENCE DAVID A.
Publication year - 2003
Publication title -
apmis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.909
H-Index - 88
eISSN - 1600-0463
pISSN - 0903-4641
DOI - 10.1034/j.1600-0463.2003.1110506.x
Subject(s) - lung , innate immune system , medicine , immunology , acquired immune system , immune system , histopathology , immunity , respiratory system , pathology
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 CO 2 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.