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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\u2009\u00b1\u2009LPS. 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 (\u00b1LPS) 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-\u03baB 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.<\/jats:p>","DOI":"10.1152\/ajplung.00506.2018","type":"journal-article","created":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T11:15:42Z","timestamp":1565781342000},"page":"L539-L549","source":"Crossref","is-referenced-by-count":10,"title":["Surfactant protein-D modulation of pulmonary macrophage phenotype is controlled by<i>S<\/i>-nitrosylation"],"prefix":"10.1152","volume":"317","author":[{"given":"Chang-Jiang","family":"Guo","sequence":"first","affiliation":[{"name":"Environmental and Occupational Health Sciences Institute, Rutgers, The State University of New Jersey, Piscataway, New Jersey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena N.","family":"Atochina-Vasserman","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Pennsylvania, Philadelphia, 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