Surfactant protein A inhibits alveolar macrophage cytokine production by CD14-independent pathway.
The lung collectin surfactant protein A (SP-A) has both anti-inflammatory and prophagocytic activities. We and others previously showed that SP-A inhibits the macrophage production of tumor necrosis factor (TNF)-alpha stimulated by the gram-negative bacterial component LPS. We propose that SP-A decreases the production of proinflammatory cytokines by alveolar macrophages via a CD14-independent mechanism. SP-A inhibited LPS-simulated TNF-alpha production in rat and mouse macrophages in the presence and absence of serum (72% and 42% inhibition, respectively). In addition, SP-A inhibited LPS-induced mRNA levels for TNF-alpha, IL-1 alpha, and IL-1 beta as well as NF-kappa B DNA binding activity. SP-A also diminished ultrapure LPS-stimulated TNF-alpha produced by wild-type and CD14-null mouse alveolar macrophages by 58% and 88%, respectively. Additionally, SP-A inhibited TNF-alpha stimulated by PMA in both wild-type and TLR4-mutant macrophages. These data suggest that SP-A inhibits inflammatory cytokine production in a CD14-independent manner and also by mechanisms independent of the LPS signaling pathway.
Alcorn
John F
JF
Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA.
Wright
Jo Rae
JR
D000818:Animals; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000378:metabolism; D037662:Pulmonary Surfactant-Associated Protein A / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D002273:Carcinogens; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D016328:NF-kappa B; D037662:Pulmonary Surfactant-Associated Protein A; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013755:Tetradecanoylphorbol Acetate