Abstract
Surfactant-associated protein A (SP-A) is involved in surfactant homeostasis and host defense in the lung. We have previously demonstrated that SP-A specifically binds to and enhances the ingestion of bacillus Calmette-Guerin (BCG) organisms by macrophages. In the current study, we investigated the effect of SP-A on the generation of inflammatory mediators induced by BCG and the subsequent fate of ingested BCG organisms. Rat macrophages were incubated with BCG in the presence and absence of SP-A. Noningested BCG organisms were removed, and the release of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide were measured at varying times. TNF-alpha and nitric oxide production induced by BCG were enhanced by SP-A. In addition, SP-A enhanced the BCG-induced increase in the level of inducible nitric oxide synthase protein. Addition of antibodies directed against SPR210, a specific macrophage SP-A receptor, inhibited the SP-A-enhanced mediator production. BCG in the absence of SP-A showed increased growth over a 5-day period, whereas inclusion of SP-A dramatically inhibited BCG growth. Inhibition of nitric oxide production blocked BCG killing in the presence and absence of SP-A. These results demonstrate that ingestion of SP-A-BCG complexes by rat macrophages leads to production of inflammatory mediators and increased mycobacterial killing.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antibodies / pharmacology
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BCG Vaccine / immunology
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Benzothiazoles
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Blotting, Western
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Cells, Cultured
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / pharmacology
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Female
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Macrophages / cytology
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Macrophages / drug effects
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Macrophages / metabolism*
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Mycobacterium tuberculosis / drug effects
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Mycobacterium tuberculosis / immunology*
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Mycobacterium tuberculosis / metabolism
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Nitric Oxide / metabolism*
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Nitric Oxide / pharmacology
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Nitric Oxide Synthase / biosynthesis
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Nitric Oxide Synthase Type II
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Proteolipids / metabolism*
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Proteolipids / pharmacology
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Pulmonary Surfactant-Associated Protein A
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Pulmonary Surfactant-Associated Proteins
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Pulmonary Surfactants / metabolism*
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Pulmonary Surfactants / pharmacology
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Rats
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Rats, Sprague-Dawley
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Thiazines / antagonists & inhibitors
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Thiazines / metabolism
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Thiazoles / antagonists & inhibitors
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Thiazoles / metabolism
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / biosynthesis
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Uracil / metabolism
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omega-N-Methylarginine / pharmacology
Substances
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Antibodies
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BCG Vaccine
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Benzothiazoles
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Enzyme Inhibitors
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Proteolipids
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Pulmonary Surfactant-Associated Protein A
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Pulmonary Surfactant-Associated Proteins
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Pulmonary Surfactants
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Thiazines
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Thiazoles
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Tumor Necrosis Factor-alpha
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SPR 210
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omega-N-Methylarginine
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Nitric Oxide
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Uracil
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, rat