Altered regulation of surfactant phospholipid and protein A during acute pulmonary inflammation.

Biochemical changes in the pulmonary surfactant system caused by exposure to toxicants are often accompanied by an influx of inflammatory cells into the lungs. We have investigated the possibility that the inflammatory and surfactant biochemical effects might be connected. Co-treatment with dexamethasone, a synthetic anti-inflammatory glucocorticoid, mitigated the increases in free cells and total intracellular surfactant phospholipid normally seen in animals given silica alone, suggesting a relationship between the free cell population of the alveoli and the surfactant system during alveolitis. Furthermore, we have investigated whether induction of the surfactant system is a universal response to alveolar inflammation. Inflammation was induced in the lungs by intratracheal injections of titanium dioxide, silica, bleomycin or lipopolysaccharide (LPS) suspended in isotonic saline. Inflammatory cell and surfactant responses were measured at 3 days and 14 days following injection. There was a distinct alveolar inflammatory cell profile following 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 exhibited 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 surfactant components and the inflammatory cell population of the alveoli undergo dynamic changes following treatment with these inflammatory agents and that activation of the surfactant system is not a universal response to alveolar inflammation, since surfactant components were not always elevated during times of increased alveolar cellularity. The unique inflammatory cell infiltrate elicited by silica is of particular 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 macrophages or lymphocytes in the alveoli following silica treatment. Finally, our data suggest that the phospholipid and SP-A components of surfactant respond differentially to the pulmonary toxicants in this study.