Study of monocyte membrane proteome perturbation during lipopolysaccharide-induced tolerance using iTRAQ-based quantitative proteomic approach

H. Zhang, C. Zhao, X. Li, Y. Zhu, C.S. Gan, Y. Wang, T. Ravasi, P.Y. Qian, S.C. Wong, S.K. Sze
Proteomics, 10(15), pp. 2780-2789, (2010)

Study of monocyte membrane proteome perturbation during lipopolysaccharide-induced tolerance using iTRAQ-based quantitative proteomic approach

Keywords

Cell biology, Endotoxin tolerance, iTRAQ, Lipopolysaccharide, Membrane proteome, Monocyte

Abstract

​Human monocytes’ exposure to low-level lipopolysaccharide (LPS) induces temporary monocytic insensitivity to subse-quent 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 down- regulated, whereas the majority of proteins from other orga-nelles 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 substantiallydecreased, 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.

Code

DOI: 10.1002/prca.201090077

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