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* Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52240;
Departments of Medicine and Molecular Virology, Immunology, and Medical Genetics, and Center for Microbial Interface Biology, and
Center for Biomedical Electron Paramagnetic Resonance Spectroscopy and Imaging, Department of Internal Medicine, Dorothy Davis Heart and Lung Research Institute, Ohio State University, Columbus, OH 43210;
Department of Internal Medicine, University of Iowa, and Department of Veterans’ Affairs, Iowa City, IA 52240; and
¶ Department of Internal Medicine, University of Cincinnati, Cincinnati, OH 45267
Alveolar macrophages are important host defense cells in the human lung that continuously phagocytose environmental and infectious particles that invade the alveolar space. Alveolar macrophages are prototypical alternatively activated macrophages, with up-regulated innate immune receptor expression, down-regulated costimulatory molecule expression, and limited production of reactive oxygen intermediates (ROI) in response to stimuli. Surfactant protein A (SP-A) is an abundant protein in pulmonary surfactant that has been shown to alter several macrophage (M
) immune functions. Data regarding SP-A effects on ROI production are contradictory, and lacking with regard to human M. In this study, we examined the effects of SP-A on the oxidative response of human M to particulate and soluble stimuli using fluorescent and biochemical assays, as well as electron paramagnetic resonance spectroscopy. SP-A significantly reduced M superoxide production in response to the phorbol ester PMA and to serum-opsonized zymosan (OpZy), independent of any effect by SP-A on zymosan phagocytosis. SP-A was not found to scavenge superoxide. We measured M oxygen consumption in response to stimuli using a new oxygen-sensitive electron paramagnetic resonance probe to determine the effects of SP-A on NADPH oxidase activity. SP-A significantly decreased M oxygen consumption in response to PMA and OpZy. Additionally, SP-A reduced the association of NADPH oxidase component p47phox with OpZy phagosomes as determined by confocal microscopy, suggesting that SP-A inhibits NADPH oxidase activity by altering oxidase assembly on phagosomal membranes. These data support an anti-inflammatory role for SP-A in pulmonary homeostasis by inhibiting M production of ROI through a reduction in NADPH oxidase activity.
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