Lipopolysaccharide-binding protein modulates hepatic damage and the inflammatory response after hemorrhagic shock and resuscitation

American Journal of Physiology. Gastrointestinal and Liver Physiology
Mark LehnertJohn J Lemasters

Abstract

Hemorrhagic shock and resuscitation cause endotoxemia and hepatocellular damage. Because lipopolysaccharide-binding protein (LBP) enhances cellular responses to endotoxin, our aim was to determine whether LBP contributes to hemorrhage/resuscitation-induced injury by comparing LBP knockout and wild-type mice. Under pentobarbital anaesthesia, wild-type and LBP-deficient mice were hemorrhaged to 30 mmHg for 3 h and then resuscitated with shed blood plus half the volume of lactated Ringer solution. Serum alanine aminotransferase (ALT) necrosis, neutrophil infiltration, and 4-hydroxynonenal by histology/cytochemistry and stress kinase activation by immunoblot analysis were then determined. ALT in wild-type mice was 2,461 +/- 383 and 1,418 +/- 194 IU/l (means +/- SE), respectively, at 2 and 6 h after resuscitation versus sham ALT of 102 +/- 6 IU/l. In LBP-deficient mice, ALT was blunted at both time points to 1,108 +/- 340 and 619 +/- 171 IU/l (P < 0.05). Liver necrosis after 6 h was also attenuated from 3.5 +/- 0.8% in wild-type mice to 1.3 +/- 0.5% in LBP-deficient mice (P < 0.05). After hemorrhage/resuscitation, neutrophil infiltration increased 71% more in wild-type than LBP knockout mice. Similarly, hepatic 4-hydroxynonenal stai...Continue Reading

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Citations

Feb 22, 2011·Regulatory Toxicology and Pharmacology : RTP·Jenny L ZhengCarole L Yauk
May 8, 2013·British Journal of Pharmacology·M MarasliogluM Lehnert
May 3, 2012·Oxidative Medicine and Cellular Longevity·B ReljaM Lehnert
Jun 22, 2012·HPB Surgery : a World Journal of Hepatic, Pancreatic and Biliary Surgery·Christoph CzernyJohn J Lemasters
Jul 14, 2012·HPB Surgery : a World Journal of Hepatic, Pancreatic and Biliary Surgery·Christoph CzernyJohn J Lemasters
Sep 19, 2012·Laboratory Investigation; a Journal of Technical Methods and Pathology·Arne GiebelerKonrad L Streetz
Sep 18, 2010·American Journal of Physiology. Gastrointestinal and Liver Physiology·G L SuS C Wang

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