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Surfactant protein-D modulation of pulmonary macrophage phenotype is controlled by S -nitrosylation.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2019 Nov 01; Vol. 317 (5), pp. L539-L549. Date of Electronic Publication: 2019 Aug 14. - Publication Year :
- 2019
-
Abstract
- Surfactant protein-D (SP-D) is a regulator of pulmonary innate immunity whose oligomeric state can be altered through S -nitrosylation to regulate its signaling function in macrophages. Here, we examined how nitrosylation of SP-D alters the phenotypic response of macrophages to stimuli both in vivo and in vitro. Bronchoalveolar lavage (BAL) from C57BL6/J and SP-D-overexpressing (SP-D OE) mice was incubated with RAW264.7 cells ± LPS. LPS induces the expression of the inflammatory genes Il1b and Nos2 , which is reduced 10-fold by SP-D OE-BAL. S -nitrosylation of the SP-D OE-BAL (SNO-SP-D OE-BAL) abrogated this inhibition. SNO-SP-D OE-BAL alone induced Il1b and Nos2 expression. PCR array analysis of macrophages incubated with SP-D OE-BAL (±LPS) shows increased expression of repair genes, Ccl20 , Cxcl1 , and Vcam1 , that was accentuated by LPS. LPS increases inflammatory gene expression, Il1a , Nos2 , Tnf , and Ptgs2 , which was accentuated by SNO-SP-D OE-BAL but inhibited by SP-D OE-BAL. The transcription factor NF-κB was identified as a target for SNO-SP-D by IPA, which was confirmed by Trans-AM ELISA in vitro. In vivo, SP-D overexpression increases the burden of infection in a Pneumocystis model while increasing cellular recruitment. Expression of iNOS and the production of NO metabolites were significantly reduced in SP-D OE mice relative to C57BL6/J. Inflammatory gene expression was increased in infected C57BL6/J mice but decreased in SP-D OE. SP-D oligomeric structure was disrupted in C57BL6/J infected mice but unaltered within SP-D OE. Thus SP-D modulates macrophage phenotype and the balance of multimeric to trimeric SP-D is critical to this regulation.
- Subjects :
- Animals
Bronchoalveolar Lavage Fluid chemistry
Bronchoalveolar Lavage Fluid immunology
Chemokine CCL20 genetics
Chemokine CCL20 immunology
Chemokine CXCL1 genetics
Chemokine CXCL1 immunology
Cyclooxygenase 2 genetics
Cyclooxygenase 2 immunology
Female
Immunity, Innate
Interleukin-1beta genetics
Interleukin-1beta immunology
Lipopolysaccharides pharmacology
Lung immunology
Lung metabolism
Lung microbiology
Macrophages, Alveolar drug effects
Macrophages, Alveolar microbiology
Male
Mice
Mice, Inbred C57BL
NF-kappa B genetics
NF-kappa B immunology
Nitric Oxide Synthase Type II genetics
Nitric Oxide Synthase Type II immunology
Nitroso Compounds immunology
Phenotype
Pneumocystis growth & development
Pneumocystis pathogenicity
Pneumocystis Infections immunology
Pneumocystis Infections metabolism
Pneumocystis Infections microbiology
Pulmonary Surfactant-Associated Protein D genetics
Pulmonary Surfactant-Associated Protein D immunology
RAW 264.7 Cells
Tumor Necrosis Factor-alpha genetics
Tumor Necrosis Factor-alpha immunology
Vascular Cell Adhesion Molecule-1 genetics
Vascular Cell Adhesion Molecule-1 immunology
Macrophages, Alveolar immunology
Nitroso Compounds metabolism
Pneumocystis Infections genetics
Protein Processing, Post-Translational
Pulmonary Surfactant-Associated Protein D metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1504
- Volume :
- 317
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 31411060
- Full Text :
- https://doi.org/10.1152/ajplung.00506.2018