S-Nitrosylation of Surfactant Protein-D Controls Inflammatory Function Export

@article{citeulike:3503499, abstract = {The pulmonary collectins, surfactant proteins A and D (SP-A and SP-D) have been implicated in the regulation of the innate immune system within the lung. In particular, SP-D appears to have both pro- and anti-inflammatory signaling functions. At present, the molecular mechanisms involved in switching between these functions remain unclear. SP-D differs in its quaternary structure from SP-A and the other members of the collectin family, such as C1q, in that it forms large multimers held together by the N-terminal domain, rather than aligning the triple helix domains in the traditional ” bunch of flowers” arrangement. There are two cysteine residues within the hydrophobic N terminus of SP-D that are critical for multimer assembly and have been proposed to be involved in stabilizing disulfide bonds. Here we show that these cysteines exist within the reduced state in dodecameric SP-D and form a specific target for S-nitrosylation both in vitro and by endogenous, pulmonary derived nitric oxide (NO) within a rodent acute lung injury model. S-nitrosylation is becoming increasingly recognized as an important post-translational modification with signaling consequences. The formation of S-nitrosothiol (SNO)-SP-D both in vivo and in vitro results in a disruption of SP-D multimers such that trimers become evident. SNO-SP-D but not SP-D, either dodecameric or trimeric, is chemoattractive for macrophages and induces p38 MAPK phosphorylation. The signaling capacity of SNO-SP-D appears to be mediated by binding to calreticulin/CD91. We propose that NO controls the dichotomous nature of this pulmonary collectin and that posttranslational modification by S-nitrosylation causes quaternary structural alterations in SP-D, causing it to switch its inflammatory signaling role. This represents new insight into both the regulation of protein function by S-nitrosylation and NO's role in innate immunity.}, author = {Guo, Chang-Jiang and Atochina-Vasserman, Elena N. and Abramova, Elena and Foley, Joseph P. and Zaman, Aisha and Crouch, Erika and Beers, Michael F. and Savani, Rashmin C. and Gow, Andrew J.}, citeulike-article-id = {3503499}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pbio.0060266}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18494562}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18494562}, day = {1}, doi = {10.1371/journal.pbio.0060266}, journal = {PLoS Biology}, keywords = {inflammation, nitric\_oxide, no, protein-d, s-nitrosylation}, month = {November}, number = {11}, pages = {e266+}, posted-at = {2008-11-11 13:08:54}, priority = {3}, title = {S-Nitrosylation of Surfactant Protein-D Controls Inflammatory Function}, url = {http://dx.doi.org/10.1371/journal.pbio.0060266}, volume = {6}, year = {2008} }

TY - JOUR ID - citeulike:3503499 L3 - citeulike-article-id:3503499 N2 - The pulmonary collectins, surfactant proteins A and D (SP-A and SP-D) have been implicated in the regulation of the innate immune system within the lung. In particular, SP-D appears to have both pro- and anti-inflammatory signaling functions. At present, the molecular mechanisms involved in switching between these functions remain unclear. SP-D differs in its quaternary structure from SP-A and the other members of the collectin family, such as C1q, in that it forms large multimers held together by the N-terminal domain, rather than aligning the triple helix domains in the traditional “bunch of flowers” arrangement. There are two cysteine residues within the hydrophobic N terminus of SP-D that are critical for multimer assembly and have been proposed to be involved in stabilizing disulfide bonds. Here we show that these cysteines exist within the reduced state in dodecameric SP-D and form a specific target for S-nitrosylation both in vitro and by endogenous, pulmonary derived nitric oxide (NO) within a rodent acute lung injury model. S-nitrosylation is becoming increasingly recognized as an important post-translational modification with signaling consequences. The formation of S-nitrosothiol (SNO)-SP-D both in vivo and in vitro results in a disruption of SP-D multimers such that trimers become evident. SNO-SP-D but not SP-D, either dodecameric or trimeric, is chemoattractive for macrophages and induces p38 MAPK phosphorylation. The signaling capacity of SNO-SP-D appears to be mediated by binding to calreticulin/CD91. We propose that NO controls the dichotomous nature of this pulmonary collectin and that posttranslational modification by S-nitrosylation causes quaternary structural alterations in SP-D, causing it to switch its inflammatory signaling role. This represents new insight into both the regulation of protein function by S-nitrosylation and NO's role in innate immunity. IS - 11 JF - PLoS Biology TI - S-Nitrosylation of Surfactant Protein-D Controls Inflammatory Function VL - 6 SP - e266 KW - inflammation KW - nitric_oxide KW - no KW - protein-d KW - s-nitrosylation AU - Guo, Chang-Jiang AU - Atochina-Vasserman, Elena AU - Abramova, Elena AU - Foley, Joseph AU - Zaman, Aisha AU - Crouch, Erika AU - Beers, Michael AU - Savani, Rashmin AU - Gow, Andrew PY - 2008/11/01/ UR - http://dx.doi.org/10.1371/journal.pbio.0060266 ER -