Abstract 410: Human SR-BI/SR-BII Overexpression Enhances LPS-induced Liver and Kidney Inflammation and Acute Organ Injury
SR-BI and its splice variant SR-BII are HDL receptors that recognize bacteria and other pathogens. It has been reported that the SR-BI/II knockout mouse is more sensitive to endotoxin-induced inflammation and sepsis. Since the SR-BI/II KO model demonstrates a number of immunity-related deficiencies and metabolic alterations, we investigated the role of each receptor in the LPS-induced inflammatory response and tissue damage using transgenic mice with LIV11-directed liver/kidney expression of hSR-BI or hSR-BII. 6 hours after intraperitoneal LPS injection transgenic hSR-BII and hSR-BI mice demonstrated markedly higher serum levels of pro-inflammatory cytokines/chemokines and 2- to 3-fold increased expression levels of inflammatory mediators in the liver and kidney, compared to WT mice. In line with the pro-inflammatory status of hSR-BI and hSR-BII transgenic mice, considerably (3-6-fold) higher expression of iNOS was detected in liver and kidney of these animals, while serum NO levels were similar in all groups of mice. Despite lower levels of plasma HDL, LPS-induced corticosterone was only moderately reduced (by 30%) in plasma of both groups of transgenic mice when compared to WT animals. Histological examination of tissues from LPS-challenged mice revealed hepatic and renal injury in hSR-BII transgenic mice, while no statistically significant changes in damage score were observed between the hSR-BI transgenic and WT mice. Our findings demonstrate that hSR-BII, and to a lesser extent hSR-BI, could substantially increase LPS-triggered inflammation and contribute to LPS-induced tissue injury in the liver and kidney, two major organs that are susceptible to LPS toxicity during sepsis.
Author Disclosures: A.V. Bocharov: None. I.N. Baranova: None. A.C.P. Souza: None. T.G. Vishnyakova: None. A.T. Remaley: None. P.S.T. Yuen: None. R.A. Star: None. A.P. Patterson: None. T.L. Eggerman: None.
- © 2015 by American Heart Association, Inc.