High Density Lipoprotein Protects against Polymicrobe-induced Sepsis in Mice |
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Authors: | Ling Guo Junting Ai Zhong Zheng Deborah A Howatt Alan Daugherty Bin Huang Xiang-An Li |
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Institution: | From the ‡Department of Pediatrics.;§Graduate Center for Nutritional Sciences.;¶Saha Cardiovascular Research Center, and ;‖Kentucky Cancer Registry, University of Kentucky College of Medicine, Lexington, Kentucky 40536 |
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Abstract: | HDL has been considered to be a protective factor in sepsis; however, most contributing studies were conducted using the endotoxic animal model, and evidence from clinically relevant septic animal models remains limited and controversial. Furthermore, little is known about the roles of HDL in sepsis other than LPS neutralization. In this study, we employed cecal ligation and puncture (CLP), a clinically relevant septic animal model, and utilized apoA-I knock-out (KO) and transgenic mice to elucidate the roles of HDL in sepsis. ApoA-I-KO mice were more susceptible to CLP-induced septic death as shown by the 47.1% survival of apoA-I-KO mice versus the 76.7% survival of C57BL/6J (B6) mice (p = 0.038). ApoA-I-KO mice had exacerbated inflammatory cytokine production during sepsis compared with B6 mice. Further study indicated that serum from apoA-I-KO mice displayed less capacity for LPS neutralization compared with serum from B6 mice. In addition, apoA-I-KO mice had less LPS clearance, reduced corticosterone generation, and impaired leukocyte recruitment in sepsis. In contrast to apoA-I-KO mice, apoA-I transgenic mice were moderately resistant to CLP-induced septic death compared with B6 mice. In conclusion, our findings reveal multiple protective roles of HDL in CLP-induced sepsis. In addition to its well established role in neutralization of LPS, HDL exerts its protection against sepsis through promoting LPS clearance and modulating corticosterone production and leukocyte recruitment. Our study supports efforts to raise HDL levels as a therapeutic approach for sepsis. |
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Keywords: | Dyslipidemia High Density Lipoprotein (HDL) Immunology Lipopolysaccharide (LPS) Sepsis Apolipoprotein A-I SCARB1 Scavenger Receptor BI Cecal Ligation and Puncture |
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