S-nitrosylation of surfactant protein D as a modulator of pulmonary inflammation

Elena N. Atochina-Vasserman

Research output: Contribution to journalReview article

24 Citations (Scopus)

Abstract

Background: Surfactant protein D (SP-D) is a member of the family of proteins termed collagen-like lectins or "collectins" that play a role in non-antibody-mediated innate immune responses [1]. The primary function of SP-D is the modulation of host defense and inflammation [2]. Scope of review: This review will discuss recent findings on the physiological importance of SP-D S-nitrosylation in biological systems and potential mechanisms that govern SP-D mediated signaling. Major conclusions: SP-D appears to have both pro- and anti-inflammatory signaling functions. SP-D multimerization is a critical feature of its function and plays an important role in efficient innate host defense. Under baseline conditions, SP-D forms a multimer in which the N-termini are hidden in the center and the C-termini are on the surface. This multimeric form of SP-D is limited in its ability to activate inflammation. However, NO can modify key cysteine residues in the hydrophobic tail domain of SP-D resulting in a dissociation of SP-D multimers into trimers, exposing the S-nitrosylated N-termini. The exposed S-nitrosylated tail domain binds to the calreticulin/CD91 receptor complex and initiates a pro-inflammatory response through phosphorylation of p38 and NF-κB activation [3,4]. In addition, the disassembled SP-D loses its ability to block TLR4, which also results in activation of NF-κB. General significance: Recent studies have highlighted the capability of NO to modify SP-D through S-nitrosylation, causing the activation of a pro-inflammatory role for SP-D [3]. This represents a novel mechanism both for the regulation of SP-D function and NO's role in innate immunity, but also demonstrates that the S-nitrosylation can control protein function by regulating quaternary structure. This article is part of a Special Issue entitled Regulation of Cellular Processes by S-nitrosylation.

Original languageEnglish
Pages (from-to)763-769
Number of pages7
JournalBiochimica et Biophysica Acta - General Subjects
Volume1820
Issue number6
DOIs
Publication statusPublished - Jun 2012
Externally publishedYes

Keywords

  • Macrophages polarization
  • Nitric oxide
  • NO
  • Pulmonary inflammation
  • S-nitrosothiol
  • SNO
  • SP-D
  • Surfactant protein D
  • TLR
  • Toll like receptor

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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