MODIFICATION BY HYPEROXIA INVIVO OF ENDOTOXIN-INDUCED NEUTROPHIL ALVEOLITIS IN RATS - PRODUCTION OF CHEMOTACTIC FACTORS BY ALVEOLAR MACROPHAGES AND ULTRASTRUCTURE

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Abstract
Prior exposure to hyperoxia intensifies the influx of polymorphonuclear leukocytes into bronchoalveolar spaces after endotoxemia (E), but the mechanism is unknown. Because pulmonary alveolar macrophages (PAM) regulate the migration of polymorphonuclear leukocytes into the lung in several types of acute and chronic alveolitis, the effect of pretreatment with hyperoxia in vivo on production of chemotactic factors by PAM after E was studied. PAM recovered by lung lavage from O2- and air-pretreated rats 4, 15 and 48 h after E were cultured to determine whether a direct effect of hyperoxia on the release of chemotactic factors by PAM in response to E in vivo could contribute to the previous observations. The chemotactic activity of the culture media supernatants from PAM recovered from O2-pretreated rats given E was 80% higher than that of media from PAM recovered from air-exposed rats given E. Neither PAM from air-exposed rats nor those from O2-exposed rats spontaneously released chemotaxins selective for other PAM. When PAM were stimulated with zymosan in vitro, those from the O2-breathing group produced 50% more chemotactic activity for other PAM than did those from the air-breathing group. These differences in secretion of chemotactic factors were not associated with decreased viability of PAM either in vivo or in tissue culture, or with impaired adherence by PAM in vitro. EM from the lungs of rats pretreated with O2, then given E, showed that lung damage was severe, and that PAM contained a large number of phagocytic lysosomes filled with amorphous electron-dense inclusion bodies and with structures resembling tubular myelin. Short-term exposure to high levels of inspired O2 affects both the structural and functional responses of alveolar macrophages to E in vivo. Functional alterations of PAM may augment the recruitment of inflammatory cells into air spaces if exposure to high inspired concentrations of O2 has occurred prior to the onset of E.