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 x 10(6)) 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.
The number of free lung-cells was studied in guinea-pigs after acute exposure to extracts of various cotton dusts. A good correlation was found between the increase in number of leucocytes in the airways and the number of Gram-negative bacteria in the different dusts. Experiments using the Shwartzmann reaction and the Limulus titration test demonstrated a relationship between the content of different endotoxins in the dusts and the pulmonary reaction. A model for the acute exposure effects after exposure to cotton dust is proposed.
Different cell types were studied in bronchoalveolar lavage fluid (BAL) and solid lung tissue of guinea-pigs. Whereas alveolar macrophages (AM) and eosinophils predominated in BAL, the proportion of AM and lymphocytes was highest in the lung tissue. After an inhalation exposure to LPS, the number of neutrophils increased rapidly in the lung tissue reaching a maximum after 4 hours, and more slowly in the airways reaching a maximum after 24 hours. This suggests that other mechanisms than secretion of chemotactic factors from AM, shown to be active up to 4 hours after exposure, are responsible for the later phase of the neutrophil invasion into the airways. Passive migration or other mediators may be involved.
Guinea-pigs were exposed to an aerosol of bacterial endotoxin (lipopolysaccharide, LPS). The free lung cell response and alveolar macrophage (AM) chemotaxis were studied. Neutrophils from guinea-pig blood gave larger migration responses than those obtained by intraperitoneal glycogen stimulation or human neutrophils. An increase in the number of neutrophils in the airways was found with a peak at 12-24 hours after exposure. In animals pre-treated with LPS inhalation for 4 months, the reaction was of shorter duration and smaller magnitude. AM showed in vitro chemotactic activity up to 4 hours after exposure; no difference was found in pre-treated animals. The results suggest that the neutrophil invasion in the airways after LPS is dependent on two mechanisms, the initial being AM chemotaxis, which is not modified by pre-exposure to LPS, and another unknown factor, which is modified by pre-exposure to LPS.
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