Surfactant protein A decreases nitric oxide production by macrophages in a tumor necrosis factor-alpha-dependent mechanism.
Surfactant protein A (SP-A) modulates the lung defense system through regulation of cytokines and nitric oxide (NO) production by alveolar macrophages (AMs). Whether SP-A upregulates or downregulates production of proinflammatory cytokines and NO is controversial. This study demonstrates the molecular mechanism(s) by which SP-A suppresses NO production by activated murine AMs. NO production by interferon-gamma (IFN-gamma) and IFN-gamma plus Mycobacterium avium-stimulated AMs was mediated through tumor necrosis factor-alpha (TNF-alpha) production, as addition of neutralizing anti-TNF-alpha antibodies during AMs stimulation resulted in reduced NO production. SP-A suppressed NO production by activated AMs by inhibiting TNF-alpha production. The maximum inhibitory effect of SP-A on NO production was observed at 20 microg/ml of SP-A concentration. Furthermore, SP-A inhibited activation of nuclear factor-kappa B, a transcription factor required for induction of TNF-alpha and inducible NO synthase genes. These findings suggest that SP-A suppresses NO production by activated AMs by inhibiting TNF-alpha secretion and nuclear factor-kappa B activation. This study also highlights the importance of SP-A levels in the lung, as changes in SP-A levels may modulate the local lung defense system.
Hussain
Shabbir
S
Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Occupational Medicine, Indiana University Medical Center, Indianapolis, USA.
Wright
Jo Rae
JR
Martin
William J
WJ
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000382:microbiology / Q000502:physiology*; D051379:Mice; D009162:Mycobacterium avium; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000378:metabolism*; D037662:Pulmonary Surfactant-Associated Protein A / Q000302:isolation & purification / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D016328:NF-kappa B; D037662:Pulmonary Surfactant-Associated Protein A; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma