- 作者：Elena N. Atochina-Vasserman ; atochina@mail.med.upenn.edu
- 关键词：TLR ; Toll-like receptor ; TIR ; Toll/IL-1 receptor domain ; LPS ; lipopolyssacharides ; LBP ; LPS-binding protein ; MD-2 ; myeloid differentiation factor 2 ; MyD88 ; myeloid differentiation protein 88 ; IRAK ; IL-1 receptor associated kinase ; TRAF6 ; TNF receptor asso
- 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
- 出版年：2012
- 出版时间：June, 2012
- 年：2012
- 卷：1820
- 期：6
- 页码：763-769
- 全文大小：727 K
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 []. The primary function of SP-D is the modulation of host defense and inflammation .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-¦ÊB activation [3,4]. In addition, the disassembled SP-D loses its ability to block TLR4, which also results in activation of NF-¦ÊB.
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.