The factors which regulate the function of alveolar macrophages in situ are incompletely understood, but surfactant components may be important. My preliminary results indicate that constituents in rat delipidated lung surfactant augment the stimulated migration of resident pulmonary alveolar macrophages in vitro and that a highly purified surfactant apoprotein has a similar effect. In addition, highly purified human surfactant apoprotein augments the chemotactic response of peripheral blood monocytes but in neither system does this surfactant material appear to have a direct effect on migration. Finally, constituents in delipidated surfactant appear to modulate the generation of superoxide anion by rat alveolar macrophages. These data suggest that components of the surfactant system, and specifically surfactant apoproteins, are essential for optimal function of resident macrophages in situ. The overall aim of this proposal is to determine what functions of alveolar macrophages, as assessed in vitro, are affected by surfactant apoproteins and the mechanism(s) by which these effects are mediated. Specifically, I propose to examine functions important in lung defenses: chemotaxis, secretion of chemotactic factors, production of superoxide anion, phagocytosis, microbicidal activity, and IgG and C3 receptor detectability. Rat and human alveolar macrophages will be tested. Also, whether surfactant specific apoprotein influences immune function of alveolar macrophages will be assessed by determining if it affects the expression of Ia like antigen on the surface membrane and the ability of the alveolar macrophage to act as an accessory cell in mitogen and antigen induced proliferation of lymphocytes. The factors inducing the differentiation of monocytes into macrophages in the lung are also incompletely understood. Therefore, another aim of this proposal is to explore how surfactant apoproteins influence the differentiation of cultured human monocytes into macrophages. To elucidate how surfactant apoprotein affects macrophages stimulated peptides, the effect of the apoprotein on receptor-mediated binding of these oligopeptides will be assessed. Binding and internalization of surfactant apoprotein by mononuclear cells will be studied using a fluorescein-labeled antibody specific for surfactant apoprotein. Results of these studies will extend the understanding of how lung surfactant apoproteins interact with the alveolar macrophage and should provide new insights into the function of this immunocompetent phagocyte within the unique environment of the lung alveolar space.
| Hoffman, R M; Dauber, J H; Paradis, I L et al. (1993) Peripheral blood monocyte migration in lung transplant recipients. Transplantation 56:228-30 |
| Hoffman, R M; Rogers, R M (1991) Serum and lavage lactate dehydrogenase isoenzymes in pulmonary alveolar proteinosis. Am Rev Respir Dis 143:42-6 |
| Hoffman, R M; Dauber, J H; Paradis, I L et al. (1991) Alveolar macrophage migration after lung transplantation. Am Rev Respir Dis 143:834-8 |
| Hoffman, R M; Dauber, J H; Rogers, R M (1989) Improvement in alveolar macrophage migration after therapeutic whole lung lavage in pulmonary alveolar proteinosis. Am Rev Respir Dis 139:1030-2 |
