title: Study of monocyte membrane proteome perturbation during lipopolysaccharide-induced tolerance using iTRAQ-based quantitative proteomic approach.
abstract: 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.
authors.affiliation: School of Biological Sciences, Nanyang Technological University, Singapore.
authors.forename: Huoming
authors.initials: H
authors.lastname: Zhang
authors.forename: Changqing
authors.initials: C
authors.lastname: Zhao
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Chee Sian
authors.initials: CS
authors.lastname: Gan
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Timothy
authors.initials: T
authors.lastname: Ravasi
authors.forename: Pei-Yuan
authors.initials: PY
authors.lastname: Qian
authors.forename: Siew Cheng
authors.initials: SC
authors.lastname: Wong
authors.forename: Siu Kwan
authors.initials: SK
authors.lastname: Sze
mesh_terms: 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
chemical_list: D008070:Lipopolysaccharides; D008565:Membrane Proteins; D020543:Proteome; D051193:Toll-Like Receptors