Cell Recruitment into Lung Wall and Airways of Conventional and Pathogen-free Guinea Pigs after Inhalation of Endotoxin

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Abstract
The cell kinetics of the acute inflammatory response to inhaled endotoxin (lipopolysaccharide, LPS) was studied in the lungs of conventional (CV) and pathogen-free (SPF) guinea pigs. Airway cells were obtained by bronchoalveolar lavage (BAL). Lung wall cells were prepared via collagenase digestion of lung tissue slices. Acute exposure to LPS triggered the influx within 4 to 12 h of equivalent numbers (approximately 70 × 106) of neutrophils into the lung walls of both CV and SPF guinea pigs. The recruited neutrophils then proceeded into the airways of CV animals, and by 48 h all recruited neutrophils were recoverable by BAL. In contrast, only one third of recruited neutrophils in the lungs of SPF animals moved from the lung wall into the airways. Analysis of neutrophil chemotactic factor (NCF) production identified lung wall cells as the major source of LPS-induced NCF activity in both groups and as virtually the sole source in SPF animals. The results emphasize the importance of studies on the precise lung tissue distribution of both recruited neutrophils, and endogenous NCF-producing cells, in elucidating the acute inflammatory response in the lungs.