Surfactant protein A differentially regulates IFN-gamma- and LPS-induced nitrite production by rat alveolar macrophages.
Although several studies have demonstrated that the pulmonary collectins surfactant protein (SP)-A and SP-D contribute to innate immunity by enhancing pathogen phagocytosis, the role of SP-A and SP-D in regulating production of free radicals and cytokines is controversial. We hypothesized that the state and mechanism of activation of the immune cell influence its response to SP-A. The effects of SP-A and SP-D on production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS) were assessed in isolated rat alveolar macrophages activated with lipopolysaccharide (LPS), interferon gamma (IFN-gamma), or both agonists. SP-A inhibited production of NO and iNOS in macrophages stimulated with smooth LPS, which did not significantly bind SP-A, or rough LPS, which avidly bound SP-A. In contrast, SP-A enhanced production of NO and iNOS in cells stimulated with IFN-gamma or INF-gamma plus LPS. Neither SP-A nor SP-D affected baseline NO production, and SP-D did not significantly affect production of NO in cells stimulated with either LPS or IFN-gamma. These results suggest that SP-A contributes to the lung inflammatory response by exerting differential effects on the responses of immune cells, depending on their state and mechanism of activation.
Stamme
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C
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Walsh
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Wright
J R
JR
D000818:Animals; D001667:Binding, Competitive; D015922:Complement C1q / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006023:Glycoproteins / Q000494:pharmacology; D007074:Immunoglobulin G / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D011510:Proteolipids / Q000378:metabolism / Q000494:pharmacology*; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
D006023:Glycoproteins; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D009569:Nitric Oxide; D015922:Complement C1q; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat