Open AccessHUMAN CHOLESTERYL ESTER TRANSFER PROTEIN EXPRESSION ENHANCES THE MOUSE SURVIVAL RATE IN AN EXPERIMENTAL SYSTEMIC INFLAMMATION MODEL
Author(s) -
P.M. Cazita,
Denise Frediani Barbeiro,
Ana Iochabel Soares Moretti,
Eder Carlos Rocha Quintão,
Francisco Garcia Soriano
Publication year - 2008
Publication title -
shock
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.095
H-Index - 117
eISSN - 1540-0514
pISSN - 1073-2322
DOI - 10.1097/shk.0b013e31816e30fd
Subject(s) - cholesterylester transfer protein , proinflammatory cytokine , chemistry , in vitro , lipoprotein , tumor necrosis factor alpha , inflammation , cholesteryl ester , wild type , endogeny , systemic inflammation , adoptive cell transfer , intraperitoneal injection , endocrinology , medicine , biology , biochemistry , immunology , cholesterol , gene , mutant , cytotoxic t cell
Mice expressing human cholesteryl ester transfer protein (huCETP) are more resistant to Escherichia coli bacterial wall LPS because death rates 5 days after intraperitoneal inoculation of LPS were higher in wild-type than in huCETP+/+ mice, whereas all huCETP+/+ mice remained alive. After LPS inoculation, plasma concentrations of TNF-alpha and IL-6 increased less in huCETP+/+ than in wild-type mice. LPS in vitro elicited lower TNF-alpha production by CETP expressing than by wild-type macrophages. In addition, TNF-alpha production by RAW 264.7 murine macrophages increased on incubation with LPS but decreased in a dose-dependent manner when human CETP was added to the medium. Human CETP in vitro enhanced the LPS binding to plasma high-density lipoprotein/low-density lipoprotein. The liver uptake of intravenous infused 14C-LPS from Salmonella typhimurium was greater in huCETP+/+ than in wild-type mice. Present data indicate for the first time that CETP is an endogenous component involved in the first line of defense against an exacerbated production of proinflammatory mediators.