ALTERED REGULATION OF SURFACTANT PHOSPHOLIPID AND PROTEIN-A DURING ACUTE PULMONARY INFLAMMATION

Biochemical changes in the pulmonary surfactant system caused by expos ure to toxicants are often accompanied by an influx of inflammatory ce lls into the lungs. We have investigated the possibility that the infl ammatory and surfactant biochemical effects might be connected. Go-tre atment with dexamethasone, a synthetic anti-inflammatory glucocorticoi d, mitigated the increases in free cells and total intracellular surfa ctant phospholipid normally seen in animals given silica alone, sugges ting a relationship between the free cell population of the alveoli an d the surfactant system during alveolitis. Furthermore, we have invest igated whether induction of the surfactant system is a universal respo nse to alveolar inflammation. Inflammation was induced in the lungs by intratracheal injections of titanium dioxide, silica, bleomycin or li popolysaccharide (LPS) suspended in isotonic saline. Inflammatory cell and surfactant responses were measured at 3 days and 14 days followin g injection. There was a distinct alveolar inflammatory cell profile f ollowing administration of each agent, at each time point, indicating a dynamic inflammatory cell population during the course of the study. Furthermore, surfactant phospholipid and protein A (SP-A) pools exhib ited unique responses to the inflammatory agents. Only silica-treated lungs maintained elevated levels of surfactant phospholipids and SP-A throughout the course of the experiment. We conclude that both the sur factant components and the inflammatory cell population of the alveoli undergo dynamic changes following treatment with these inflammatory a gents and that activation of the surfactant system is not a universal response to alveolar inflammation, since surfactant components were no t always elevated during times of increased alveolar cellularity. The unique inflammatory cell infiltrate elicited by silica is of particula r interest in that surfactant components were elevated throughout the course of the experiment in this group. Indeed, we have shown that the size of the intracellular pool of surfactant Is directly proportional to the number of polymorphonuclear leukocytes but not alveolar macrop hages or lymphocytes in the alveoli following silica treatment. Finall y, our data suggest that the phospholipid and SP-A components of surfa ctant respond differentially to the pulmonary toxicants in this study.