| Pulmonary surfactant, a mixture of lipids and proteins, serves to defend the host against infection and prevent the collapse of the alveoli. Surfactant phospholipids and surfactant proteins (SP) SP-B and SP-C reduce surface tension, whereas SP-A and SP-D defend the host against infection. Maintenance of adequate surfactant pools through synthesis, secretion, and clearance is required for proper lung function. Surfactant homeostasis may be particularly important following lung injury, since surfactant levels are altered in lung disease and in animal models of acute lung injury.; I hypothesized that alveolar macrophages and inflammatory neutrophils, which are recruited into the lung during inflammation, contribute to the degradation clearance of surfactant. In vitro studies demonstrated that alveolar macrophages degrade two important surfactant lipids, dipalmitoylphosphatidylcholine and phosphatidylglycerol by processes that are activated by SP-A and adherence to a surface. To evaluate the role of neutrophils and macrophages from the injured lung surfactant metabolism, acute lung injury was induced by intratracheal lipopolysaccharide (LPS) instillation, resulting in a 12-fold increase in lavage cells, the majority of which were neutrophils. Macrophages isolated from LPS treated lungs were stimulated for in vitro lipid uptake and degradation, compared to cells isolated from healthy lungs. Neutrophils isolated from LPS-treated lungs were also internalized and degraded surfactant-like lipids in an SP-A dependent manner.; Although our and others in vitro data support a role for SP-A in surfactant metabolism, healthy mice deficient in SP-A have normal surfactant phospholipid levels. We hypothesized that SP-A regulated surfactant metabolism in injured lung. Intratracheal LPS instillation into SP-A (+/+) and SP-A (−/−) mice resulted in a 1.6-fold increase in lavage phospholipids in SP-A (−/−) mice and a 40% decrease in phospholipid clearance compared to SP-A (+/+) mice. Both defects were rescued by instillation of exogenous SP-A.; These data support a role for inflammatory cells in surfactant metabolism, and also demonstrate a role for SP-A in mediating phospholipid clearance following acute lung injury. |
