title: S-nitrosylation of surfactant protein D as a modulator of pulmonary inflammation.
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].
  
  
  METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Pulmonary, Allergy and Critical Care Division, Department of Medicine University of Pennsylvania, Vernon and Shirley Hill Pavilion, #H410C, 380 S. University Ave., Philadelphia, PA 19104-4539, USA. atochina@mail.med.upenn.edu
authors.forename: Elena N
authors.initials: EN
authors.lastname: Atochina-Vasserman
mesh_terms: D000818:Animals; D037282:Calreticulin / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000378:metabolism*; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000502:physiology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D015538:Nitrosation; D010766:Phosphorylation; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D037663:Pulmonary Surfactant-Associated Protein D / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D037282:Calreticulin; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D016328:NF-kappa B; D037663:Pulmonary Surfactant-Associated Protein D; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D048051:p38 Mitogen-Activated Protein Kinases