Milk fat globule EGF factor 8 attenuates sepsis-induced apoptosis and organ injury in alcohol-intoxicated rats.

Abstract

BACKGROUND:

Despite advances in our understanding of excessive alcohol-intake-related tissue injury and modernization of the management of septic patients, high morbidity and mortality caused by infectious diseases in alcohol abusers remain a prominent challenge. Our previous studies have shown that milk fat globule epidermal growth factor-factor VIII (MFG-E8), a protein required to opsonize apoptotic cells for phagocytosis, is protective in inflammation. However, it remains unknown whether MFG-E8 ameliorates sepsis-induced apoptosis and organ injury in alcohol-intoxicated rats. The purpose of this study was to determine whether recombinant murine MFG-E8 (rmMFG-E8) attenuates organ injury after acute alcohol exposure and subsequent sepsis.

METHODS:

Acute alcohol intoxication was induced in male adult rats by a bolus injection of intravenous alcohol at 1.75 g/kg BW, followed by an intravenous infusion of 300 mg/kg BW/h of alcohol for 10 hours. Sepsis was induced at the end of 10-hour alcohol infusion by cecal ligation and puncture (CLP). rmMFG-E8 or vehicle (normal saline) was administered intravenously 3 times (i.e., at the beginning of alcohol injection, the beginning of CLP, and 10 hours post-CLP) at a dose of 20 microg/kg BW each. Blood and tissue samples were collected 20 hours after CLP in alcoholic animals for various measurements.

RESULTS:

Acute alcohol exposure per se did not affect the production of MFG-E8; however, it primed the animal and enhanced sepsis-induced MFG-E8 downregulation in the spleen. Administration of rmMFG-E8 reduces alcohol/sepsis-induced apoptosis in the spleen, lungs, and liver. In addition, administration of rmMFG-E8 after alcohol exposure and subsequent sepsis decreases circulating levels of TNF-alpha and interleukin-6 and attenuates organ injury.

CONCLUSIONS:

rmMFG-E8 attenuates sepsis-induced apoptosis and organ injury in alcohol-intoxicated rats.

• Authors: Rongqian Wu, Wayne W Chaung, Mian Zhou, Youxin Ji, Weifeng Dong, Zhimin Wang, Xiaoling Qiang, Ping Wang
• Journal: Alcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 34 Issue 9 Pg. 1625-33 (Sep 01 2010) ISSN: 1530-0277 [Electronic] England
• PMID: 20586751 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antigens, Surface
• Interleukin-6
• Mfge8 protein, mouse
• Milk Proteins
• Recombinant Proteins
• Tumor Necrosis Factor-alpha

Topics

• Alcoholic Intoxication (blood, metabolism, pathology, prevention & control)
• Animals
• Antigens, Surface (metabolism, pharmacology)
• Apoptosis (drug effects)
• Down-Regulation (drug effects)
• Interleukin-6 (blood)
• Liver (drug effects, pathology)
• Lung (drug effects, pathology)
• Male
• Milk Proteins (metabolism, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Recombinant Proteins (pharmacology)
• Sepsis (blood, metabolism, pathology)
• Spleen (drug effects, metabolism, pathology)
• Tumor Necrosis Factor-alpha (blood)