Oxygen is an essential element of therapy for most neonatal lung diseases. Its usage has been implicated in lung injury and the pathogenesis of chronic neonatal lung disorders. However, no data exist regarding its effects on developing pulmonary defenses. Prior adult animal investigations suggest that oxygen administration, oxygen deprivation and hypercarbia can individually alter humoral or cellular respiratory defenses. Hyperoxia, hypoxia and hypercarbia, either singly or in combination, frequently occur in the ill human fetus and newborn. Utilizing techniques developed in our laboratories to ascertain in vivo and in vitro alveolar macrophage (AM) function, we propose to study adverse effects of the three preceding parameters in the fetal and newborn rabbit lung. Neonatal rabbits will be subjected to acute or chronic hyperoxia plus or minus hypercarbia, and the fetal rabbits will be exposed to hypoxia plus or minus hypercarbia. Conditions were selected which simulate environments to which human neonates might be exposed. Following these exposures, we will correlate in vivo alveolar macrophage function with in vitro microbicidal mechanisms of lavaged cells of treated animals. These measurements will be compared with non-exposed neonatal rabbits. In vivo studies will measure mucociliary and cellular clearance of radiolabelled Staphylococcus aureus in the left lung following simultaneous aerosol infection of treated and control animals. The right lung will be used to ascertain bacterial ingestion and digestion rates by the newborn AM. In vitro investigations of lavaged cells will examine O2-dependent (superoxide anion production and O2 consumption) and O2-independent (lysosomal enzyme, lysozyme and cationic peptide concentrations) microbicidal mechanisms of treated and control neonates. This project offers the unique opportunity to correlate in vivo function with in vitro cellular capacity. This proposal is an extension of our long-term goal of characterizing newborn lung macrophage physiology and developmental abnormalities which predispose the newborn to pulmonary bacterial infections.
| Sherman, M P; D'Ambola, J B; Aeberhard, E E et al. (1988) Surfactant therapy of newborn rabbits impairs lung macrophage bactericidal activity. J Appl Physiol 65:137-45 |
| Sherman, M P; Evans, M J; Campbell, L A (1988) Prevention of pulmonary alveolar macrophage proliferation in newborn rabbits by hyperoxia. J Pediatr 112:782-6 |
| Evans, M J; Sherman, M P; Campbell, L A et al. (1987) Proliferation of pulmonary alveolar macrophages during postnatal development of rabbit lungs. Am Rev Respir Dis 136:384-7 |
| Sherman, M P; Condiotti, R (1987) Hyperoxia damages phagocytic defenses of neonatal rabbit lung. J Appl Physiol 62:684-90 |
| Ganz, T; Sherman, M P; Selsted, M E et al. (1985) Newborn rabbit alveolar macrophages are deficient in two microbicidal cationic peptides, MCP-1 and MCP-2. Am Rev Respir Dis 132:901-4 |
| Sherman, M P; Lehrer, R I (1985) Oxidative metabolism of neonatal and adult rabbit lung macrophages stimulated with opsonized group B streptococci. Infect Immun 47:26-30 |
