The goals of this proposal are to elaborate the roles played by the type II alveolar epithelial cell and the surfactant it produces in normal host defense function in the alveolus, as well as in an immunosuppressed host and in the context of a challenge by an opportunistic pathogen, Pneumocystis carinii. Specifically, the expression of surfactant and class II major histocompatibility group (MHC) antigens at the RNA and protein levels will be characterized in type II cells and in lung tissue from normal and glucocorticoid-immunosuppressed rats using biochemical and histological techniques. Reciprocal regulatory influences between immune cells in the alveolus and the type II cell and its products will also be studied. Subsequently, the ability of the type II cell to participate in specific steps in the host defense process by serving as an antigen-presenting cell and by regulating lymphocyte proliferation will be investigated. In addition, this alveolar immune network will be examined in the context of the Pneumocystis carinii to determine how this pathogen influences the function of type II cells and their production of surfactant in a host with normal immune function. Finally, the interaction of type II cells, surfactant and immune cells with Pneumocystis will be monitored as immune function declines during immunosuppression and as it is gradually restored following the cessation of immunosuppressive steroid treatment. Defining the details of this alveolar immune network will improve our understanding of the mechanisms used by the lung to combat infections and provide insight into the reasons behind the susceptibility of the lung to Pneumocystis carinii and other opportunistic pathogens in various immunodeficiency states such as AIDS.
| Koziel, H; Phelps, D S; Fishman, J A et al. (1998) Surfactant protein-A reduces binding and phagocytosis of pneumocystis carinii by human alveolar macrophages in vitro. Am J Respir Cell Mol Biol 18:834-43 |
| Phelps, D S; Umstead, T M; Rose, R M et al. (1996) Surfactant protein-A levels increase during Pneumocystis carinii pneumonia in the rat. Eur Respir J 9:565-70 |
| Kremlev, S G; Umstead, T M; Phelps, D S (1994) Effects of surfactant protein A and surfactant lipids on lymphocyte proliferation in vitro. Am J Physiol 267:L357-64 |
| Kremlev, S G; Phelps, D S (1994) Surfactant protein A stimulation of inflammatory cytokine and immunoglobulin production. Am J Physiol 267:L712-9 |
