THE INFLUENCE OF POLYMORPHONUCLEAR LEUKOCYTES ON ALTERED PULMONARY EPITHELIAL PERMEABILITY DURING OZONE EXPOSURE

Ozone (O-3), a pulmonary irritant, and a major toxic component of phot ochemical smog, is capable of inducing pulmonary inflammation characte rized by recruitment of polymorphonuclear leukocytes (PMNs) into the l ung. The recruited PMNs, in turn, can release toxic mediators and prod uce lung injury. The mechanism of ozone-induced changes in lung permea bility remains unknown. It is our hypothesis that PMNs migrating into the lung play a significant role in the pathophysiology following O-3 exposure and that increasing the number of PMNs coming into the lung w ill exaggerate the changes in lung permeability. To test this hypothes is, we induced an influx of PMNs into the lungs of Sprague-Dawley rats by intratracheal instillation of 1% rabbit serum and then exposed the animals to either 0.8 ppm O-3 or filtered air for 3 h. Control animal s were intratracheally instilled with phosphate-buffered saline (PBS) and simultaneously exposed to O-3 or filtered air in the same manner a s the serum-treated animals. The animals were sacrificed and the lungs lavaged 10-12 h after exposure. The bronchoalveolar lavage fluid (BAL F) was analyzed for albumin and protein, as indicators of permeability . In addition, BALF from the various groups was tested for its ability to alter epithelial resistance of pulmonary type II cells in culture. O-3 exposure resulted in a significant increase in albumin and protei n levels in the BALF as compared to air-exposed controls. The instilla tion of serum resulted in a significant increase in airway PMNs, but n o significant elevations in albumin levels in both the O-3 and air-exp osed groups, as compared to PBS instillation. In vitro studies did not reveal a differential BALF effect on epithelal resistance. The data d emonstrate that an excessive neutrophilia in the lung is not matched b y a comparable amplification of epithelial injury. It is therefore sug gested that a simple elevation in PMN number in the air spaces, as tha t induced by serum instillation, does not necessarily augment the lung pathophysiology, but that a more complex interaction with O-3 may be required for cellular activation and release of toxic products. (C) 19 98 Elsevier Science Ireland Ltd. All rights reserved.