Acute ozone-induced change in airway permeability: role of infiltrating leukocytes.
The role of infiltrating polymorphonuclear leukocytes (PMNs) in acute lung injury and inflammation is still controversial. In inbred mice, acute ozone (O3) exposure induces airway inflammation that is characterized by a maximal influx of lavageable PMNs 6 h after exposure and a maximal increase in lung permeability 24 h after O3. We tested the hypothesis that O3-induced change in airway epithelial permeability of O3-susceptible C57BL/6J mice is due to infiltrating PMNs. Male mice (6-8 wk) were treated with a nonsteroidal anti-inflammatory drug (indomethacin), a chemotactic inhibitor (colchicine), or an immunosuppressant (cyclophosphamide) to deplete or inhibit PMNs from infiltrating the airways. After drug or vehicle treatment, mice were exposed for 3 h to 2 ppm O3 or filtered air, and pulmonary inflammation was assessed by inflammatory cell counts and total protein content (a marker of airway permeability) in bronchoalveolar lavage (BAL) fluid. Filtered air exposure did not affect the parameters of pulmonary inflammation at any time after exposure. Compared with vehicle controls, each of the drug treatments resulted in significant reduction of PMN influx 6 and 24 h after O3. However, total BAL protein content was not attenuated significantly by the three treatments at either 6 or 24 h postexposure. Results of these experiments suggest that the influx of PMNs and the change in total BAL protein are not mutually dependent events in this model and suggest that infiltrating PMNs do not play a major role in acute O3-induced changes in permeability of the murine lung.
Kleeberger
S R
SR
Department of Environmental Health Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Hudak
B B
BB
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D055370:Lung Injury; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D010126:Ozone / Q000633:toxicity*; D010539:Permeability / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced; D011506:Proteins / Q000378:metabolism
D011506:Proteins; D010126:Ozone; D003520:Cyclophosphamide; D003078:Colchicine; D007213:Indomethacin