Surfactant Protein-D Modulation of Pulmonary Macrophage Phenotype is Controlled by S-Nitrosylation.

Surfactant Protein-D Modulation of Pulmonary Macrophage Phenotype is Controlled by S-Nitrosylation. Am J Physiol Lung Cell Mol Physiol. 2019 Aug 14;: Authors: Guo C, Atochina-Vasserman EN, Abramova E, Smith LC, Beers MF, Gow AJ Abstract Surfactant protein-D (SP-D), 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 C57/Bl6 and SP-D overexpressing (SP-D OE) mice was incubated with RAW264.7 cells ± LPS. LPS induces expression of 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, which was accentuated by LPS. LPS increases inflammatory gene expression, IL1A, NOS2, TNF and PTGS2, that was accentuated by SNO-SP-D OE-BAL but inhibited by SP-D OE-BAL. The transcription factor NF-kB 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 cellu...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research