Study of monocyte membrane proteome perturbation during lipopolysaccharide-induced tolerance using iTRAQ-based quantitative proteomic approach.
Human monocytes' exposure to low-level lipopolysaccharide (LPS) induces temporary monocytic insensitivity to subsequent LPS challenge. The underlying mechanism of this phenomenon could have important clinical utilities in preventing and/or treating severe infections. In this study, we used an iTRAQ-based quantitative proteomic approach to comprehensively characterize the membrane proteomes of monocytes before and after LPS exposure. We identified a total of 1651 proteins, of which 53.6% were membrane proteins. Ninety-four percent of the proteins were quantified and 255 proteins were shown to be tightly regulated by LPS. Subcellular location analysis revealed organelle-specific response to LPS exposure: more than 90% of identified mitochondrial membrane proteins were significant downregulated, whereas the majority of proteins from other organelles such as ER, Golgi and ribosome were upregulated. Moreover, we found that the expression of most receptors potentially involved in LPS signal pathway (CD14, toll-like receptor 4, CD11/CD18 complex) were substantially decreased, while the expression of molecules involved in LPS neutralization were enhanced after LPS challenge. Together, these findings could be of significance in understanding the mechanism of LPS tolerance and provide values for designing new approaches for regulating monocytic responses in sepsis patients.
Zhang
Huoming
H
School of Biological Sciences, Nanyang Technological University, Singapore.
Zhao
Changqing
C
Li
Xin
X
Zhu
Yi
Y
Gan
Chee Sian
CS
Wang
Yong
Y
Ravasi
Timothy
T
Qian
Pei-Yuan
PY
Wong
Siew Cheng
SC
Sze
Siu Kwan
SK
D004721:Endoplasmic Reticulum / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000276:immunology*; D040901:Proteomics / Q000379:methods*; D012270:Ribosomes / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology
D008070:Lipopolysaccharides; D008565:Membrane Proteins; D020543:Proteome; D051193:Toll-Like Receptors