The importance of pulmonary macrophages in the lung is increasingly evident. Not only do they ingest and kill pathogens but their secretory products regulate the activities of lymphocytes, fibroblasts, neutrophils, and other cells. Changes in the renewal of lung macrophages are related to environmental stimuli. We have identified an antigen specific for pulmonary macrophages in hamsters and have shown that this antigen develops only after these cells appear on the alveolar surface. We have produce monoclonal antibodies to this antigen and have developed methods to quantify antigen on individual cells using fluorescence activated flow cytometry and sorting. The purpose of this research is to describe pulmonary macrophage heterogeniety, function and differentiation using this antigen and our monoclonals as investigative tools. We will correlate the amount of antigen on lung macrophages with parameters of macrophage differentiation and function in normal adults animals. In addition, we will make these correlations in fetal and neonatal lungs as well as in adult animal lungs altered by infection and interestitial inflammatory lung disease. Since we have found that our monoclonal antibody can specifically inhibit ingestion of albumin coated latex beads, we will continue in vitro studies of factors which regulate differentiation with emphasis on the role of this antigen in phagocytosis. Finally, we intend to use our monoclonal antibody in vivo to deplete and/or block pulmonary macrophage actions to define other defensive mechanisms available to the lung when macrophages are rendered non-functional.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Pathology A Study Section (PTHA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard University
Schools of Dentistry/Oral Hygn
United States
Zip Code
Huang, S; Paulauskis, J D; Godleski, J J et al. (1992) Expression of macrophage inflammatory protein-2 and KC mRNA in pulmonary inflammation. Am J Pathol 141:981-8
Kobzik, L; Godleski, J J; Brain, J D (1990) Selective down-regulation of alveolar macrophage oxidative response to opsonin-independent phagocytosis. J Immunol 144:4312-9
Kreyling, W G; Godleski, J J; Kariya, S T et al. (1990) In vitro dissolution of uniform cobalt oxide particles by human and canine alveolar macrophages. Am J Respir Cell Mol Biol 2:413-22
Kobzik, L; Godleski, J J; Brain, J D (1990) Oxidative metabolism in the alveolar macrophage: analysis by flow cytometry. J Leukoc Biol 47:295-303
Sorokin, S P; Kobzik, L; Hoyt Jr, R F et al. (1989) Development of surface membrane characteristics of ""premedullary"" macrophages in organ cultures of embryonic rat and hamster lungs. J Histochem Cytochem 37:365-76
Kobzik, L; Godleski, J J; Barry, B E et al. (1988) Isolation and antigenic identification of hamster lung interstitial macrophages. Am Rev Respir Dis 138:908-14
Parod, R J; Brain, J D (1986) Immune opsonin-independent phagocytosis by pulmonary macrophages. J Immunol 136:2041-7
Parod, R J; Godleski, J J; Brain, J D (1986) Inhibition of immune opsonin-independent phagocytosis by antibody to a pulmonary macrophage cell surface antigen. J Immunol 136:2048-54
Kobzik, L; Godleski, J J; Brain, J D (1985) Ultrastructural analysis of a specific hamster alveolar macrophage antigen. Lab Invest 53:526-33
Kobzik, L; Godleski, J J; Biondi, A et al. (1985) Immunohistologic analysis of a human pulmonary alveolar macrophage antigen. Clin Immunol Immunopathol 37:213-9