Abstract 5539: Human CETP Expression Promotes The Plasma Clearance And Hepatic Uptake Of Lipopolysaccharide
Background: Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that plays a role in the reverse cholesterol transport system for transferring cholesteryl ester from HDL to triglyceride-rich lipoproteins. The precise role of CETP in atherogenesis has been controversial because of divergent effects of CETP on the incidence or development of atherosclerotic disease in humans and animals. Structural and physiological similarities exist between CETP and the lipopolysaccharide-binding protein (LBP), its involvement in the cascade of TLR4-mediated events is likely. The aim of this work was to study the role of huCETP in the host defense system.
Methods: Smooth LPS from Salmonella typhimurium (strain PR122, kindly provided by Dr. Robert Munford, Internal Medicine and Microbiology, UT Southwestern Medical Center 5323, Dallas, TX) was labeled with 3H in the galactose moiety. Lipopolysaccharide (LPS) was diluted into 300 microliters of PBS, 1 mM EDTA, 100 micrograms/ml of BSA and vortex vigorously. The solution containing about 1 microgram of LPS/10 μL. Mice expressing human cholesteryl ester transfer protein (huCETP) and wild type (CETP−/−) were infused in the femoral vein 3H-LPS (500,000 dpm) and sacrificed at 24h. The tissue uptake and plasma removal rates of 3H-LPS were compared between groups. Liver, spleen, kidney, lung and heart were minced in PBS (1% Triton X-100) and an aliquot utilized for radioactivity counting in beta scintillation counter.
Results: The clearance of 3H-LPS from plasma was much faster in huCETP expressing than wild type mice, P < 0.001. In addition, the liver uptake was increased CETP as compare WT mice P < 0.001. On the other hand, there were not difference in spleen, kidney, lung and heart.
Conclusions: These experiments show that CETP expression promotes the removal of plasma LPS and increases the uptake in the liver. Our results indicate that CETP is an endogenous component involved in the first line defense system of innate immunity.