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Study of monocyte membrane proteome perturbation during lipopolysaccharide‐induced tolerance using iTRAQ‐based quantitative proteomic approach
Author(s) -
Zhang Huoming,
Zhao Changqing,
Li Xin,
Zhu Yi,
Gan Chee Sian,
Wang Yong,
Ravasi Timothy,
Qian PeiYuan,
Wong Siew Cheng,
Sze Siu Kwan
Publication year - 2010
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201000066
Subject(s) - lipopolysaccharide , proteome , cd14 , microbiology and biotechnology , membrane protein , quantitative proteomics , biology , downregulation and upregulation , proteomics , receptor , bacterial outer membrane , tlr4 , golgi apparatus , organelle , signal transduction , chemistry , endoplasmic reticulum , biochemistry , immunology , membrane , escherichia coli , gene
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.