Hepatic scavenger receptor BI protects against polymicrobial-induced sepsis through promoting LPS clearance in mice.
Recent studies revealed that scavenger receptor BI (SR-BI or Scarb1) plays a critical protective role in sepsis. However, the mechanisms underlying this protection remain largely unknown. In this study, using Scarb1(I179N) mice, a mouse model specifically deficient in hepatic SR-BI, we report that hepatic SR-BI protects against cecal ligation and puncture (CLP)-induced sepsis as shown by 75% fatality in Scarb1(I179N) mice, but only 21% fatality in C57BL/6J control mice. The increase in fatality in Scarb1(I179N) mice was associated with an exacerbated inflammatory cytokine production. Further study demonstrated that hepatic SR-BI exerts its protection against sepsis through its role in promoting LPS clearance without affecting the inflammatory response in macrophages, the glucocorticoid production in adrenal glands, the leukocyte recruitment to peritoneum or the bacterial clearance in liver. Our findings reveal hepatic SR-BI as a critical protective factor in sepsis and point out that promoting hepatic SR-BI-mediated LPS clearance may provide a therapeutic approach for sepsis.
From the Department of Pediatrics, Saha Cardiovascular Research Center.
Ling
L
Guo
From the Department of Pediatrics, Graduate Center for Nutritional Sciences, and.
Zhong
Z
Zheng
From the Department of Pediatrics, Graduate Center for Nutritional Sciences, and.
Junting
J
Ai
Kentucky Cancer Registry, University of Kentucky College of Medicine, Lexington, Kentucky 40536.
Bin
B
Huang
From the Department of Pediatrics, Saha Cardiovascular Research Center, Kentucky Cancer Registry, University of Kentucky College of Medicine, Lexington, Kentucky 40536 xli2@email.uky.edu.
Xiang-An
XA
Li
D000311:Adrenal Glands / Q000276:immunology / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002432:Cecum / Q000601:surgery; D002460:Cell Line; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005938:Glucocorticoids / Q000096:biosynthesis / Q000276:immunology; D007113:Immunity, Innate / Q000235:genetics / Q000276:immunology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008026:Ligation / Q000009:adverse effects; D008070:Lipopolysaccharides / Q000276:immunology*; D008099:Liver / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010537:Peritoneum / Q000276:immunology / Q000378:metabolism; D017354:Point Mutation; D011677:Punctures / Q000009:adverse effects; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018805:Sepsis / Q000209:etiology / Q000276:immunology* / Q000382:microbiology
D016207:Cytokines; D005938:Glucocorticoids; D008070:Lipopolysaccharides; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B
High Density Lipoprotein (HDL); Immunology; Lipopolysaccharide (LPS); Lipoprotein Receptor; SR-BI; Scarb1; Sepsis