TOLERANCE TO PHOSGENE IS ASSOCIATED WITH A NEUTROPHILIC INFLUX INTO THE RAT LUNG

Exposures to 100% oxygen, ozone, nitrogen oxides, and phosgene increas e both lung lavage protein concentrations and neutrophils. The inhibit ion of the neutrophil influx can diminish ravage protein concentration s after exposures to these oxidant gases. Similarly, this injury can b e reduced by preexposure to either the same (tolerance) or a different (cross-tolerance) oxidant gas. We tested the hypothesis that diminish ed injury after the development of tolerance to phosgene (COCl2) is as sociated with a decreased incursion of neutrophils. Sixty-day-old rats (n = 12/group) were exposed to varying concentrations of COCl2. Lung lavage (n = 6/group) 24 h after a first phosgene exposure demonstrated an increase in both protein concentrations and percentage neutrophils . The remaining animals (n = 6/group) were exposed to COCl2 2 ppm x 60 min 1 wk later. Lavage confirmed the development of tolerance with pr otein concentrations diminished after the second exposure in those rat s that had inhaled higher doses of COCl2 during the first exposure. Ho wever, the neutrophilic influx was not diminished but rather was incre ased. The association of the neutrophil incursion with a protective ef fect was further established in studies employing colchicine and dextr an. Colchicine decreased neutrophil influx occurring after the first e xposure and subsequently diminished the development of tolerance after a second exposure. Intratracheal instillation of dextran produced a n eutrophil incursion and subsequently decreased injury after a phosgene exposure. In investigations using both colchicine and dextran, neutro phil influx increased with the development of adaptation. Thus, lung i njury after the development of tolerance to phosgene provides a unique animal model of a respiratory distress syndrome in which neutrophils are not associated with injury but rather with a protective effect.