S-nitrosylation of surfactant protein-D controls inflammatory function

Chang Jiang Guo, Elena N. Atochina-Vasserman, Elena Abramova, Joseph P. Foley, Aisha Zaman, Erika Crouch, Michael F. Beers, Rashmin C. Savani, Andrew J. Gow

Research output: Contribution to journalArticle

99 Citations (Scopus)

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 Snitrosylation and NO's role in innate immunity.

Original languageEnglish
Article numbere266
Pages (from-to)2414-2423
Number of pages10
JournalPLoS Biology
Volume6
Issue number11
DOIs
Publication statusPublished - Nov 2008
Externally publishedYes

Fingerprint

Pulmonary Surfactant-Associated Protein D
surfactants
lungs
post-translational modification
proteins
Collectins
S-Nitrosothiols
nitric oxide
cysteine
calreticulin
disulfide bonds
mitogen-activated protein kinase
Post Translational Protein Processing
phosphorylation
macrophages
rodents
Lung
Cysteine
Nitric Oxide
flowers

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Guo, C. J., Atochina-Vasserman, E. N., Abramova, E., Foley, J. P., Zaman, A., Crouch, E., ... Gow, A. J. (2008). S-nitrosylation of surfactant protein-D controls inflammatory function. PLoS Biology, 6(11), 2414-2423. [e266]. https://doi.org/10.1371/journal.pbio.0060266

S-nitrosylation of surfactant protein-D controls inflammatory function. / Guo, Chang Jiang; Atochina-Vasserman, Elena N.; Abramova, Elena; Foley, Joseph P.; Zaman, Aisha; Crouch, Erika; Beers, Michael F.; Savani, Rashmin C.; Gow, Andrew J.

In: PLoS Biology, Vol. 6, No. 11, e266, 11.2008, p. 2414-2423.

Research output: Contribution to journalArticle

Guo, CJ, Atochina-Vasserman, EN, Abramova, E, Foley, JP, Zaman, A, Crouch, E, Beers, MF, Savani, RC & Gow, AJ 2008, 'S-nitrosylation of surfactant protein-D controls inflammatory function', PLoS Biology, vol. 6, no. 11, e266, pp. 2414-2423. https://doi.org/10.1371/journal.pbio.0060266
Guo, Chang Jiang ; Atochina-Vasserman, Elena N. ; Abramova, Elena ; Foley, Joseph P. ; Zaman, Aisha ; Crouch, Erika ; Beers, Michael F. ; Savani, Rashmin C. ; Gow, Andrew J. / S-nitrosylation of surfactant protein-D controls inflammatory function. In: PLoS Biology. 2008 ; Vol. 6, No. 11. pp. 2414-2423.
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