Alveolar neutrophils in endotoxin-induced and bacteria-induced acute lung injury in rats.
Polymorphonuclear neutrophils (PMNs) are thought to play a major role in the pathogenesis of adult respiratory distress syndrome. Because the alveolar epithelium is a decisive factor in alveolo-capillary wall permeability, a toxic effect of emigrated PMNs in alveolar spaces is conceivable. We evaluated alveolar PMN function in two rat models of acute lung injury induced by alveolar instillation of endotoxin [lipopolysaccharide (LPS)] or live Pseudomonas aeruginosa (PYO). Alveolar PMNs were isolated from bronchoalveolar lavage fluid 4 and 24 h after the challenge. Hypoxemia was assessed based on the ratio arterial partial pressure of O2 (PaO2)/fraction of inspired O2 (FIO2) during mechanical ventilation. The severity of lung injury in the two models was clearly different, since PaO2/FIO2 were approximately 400 mmHg in PYO- and LPS-induced injuries, respectively. Both contrast, alveolar neutrophil influx, unstimulated oxygen metabolite production, and proteinase (elastase, gelatinase B) secretions of ex vivo alveolar PMNs were not larger in the PYO model. Thus the difference in severity was not associated with variations in alveolar neutrophil recruitment or activation. Moreover, gelatinase and leukocyte elastase activities were absent in bronchoalveolar fluid, indicating effective antiproteinase defense in alveolar spaces. We conclude that alveolar neutrophils are not sufficient to create severe respiratory failure.
Delclaux
C
C
Institut National de la Santé et de la Recherche Médicale, Unité 296, Hôpital Henri Mondor, Créteil, France.
Rezaiguia-Delclaux
S
S
Delacourt
C
C
Brun-Buisson
C
C
Lafuma
C
C
Harf
A
A
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D017364:Collagenases / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity*; D005089:Exocytosis; D019272:Leukocyte Elastase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D055370:Lung Injury; D008297:Male; D020780:Matrix Metalloproteinase 9; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D011550:Pseudomonas aeruginosa; D011650:Pulmonary Alveoli / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004731:Endotoxins; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019272:Leukocyte Elastase; D017364:Collagenases; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate