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.
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 murineMFG-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: Richard S Hotchkiss; Stephen B Osmon; Katherine C Chang; Tracey H Wagner; Craig M Coopersmith; Irene E Karl Journal: J Immunol Date: 2005-04-15 Impact factor: 5.422
Authors: Kavin G Shah; Rongqian Wu; Asha Jacob; Ernesto P Molmenti; Jeffrey Nicastro; Gene F Coppa; Ping Wang Journal: Intensive Care Med Date: 2011-09-23 Impact factor: 17.440
Authors: Fangming Zhang; Kavin G Shah; Lei Qi; Rongqian Wu; Rafael Barrera; Jeffrey Nicastro; Gene F Coppa; Ping Wang Journal: J Trauma Acute Care Surg Date: 2012-04 Impact factor: 3.313
Authors: Benyam P Yoseph; Elise Breed; Christian E Overgaard; Christina J Ward; Zhe Liang; Maylene E Wagener; Daniel R Lexcen; Elizabeth R Lusczek; Greg J Beilman; Eileen M Burd; Alton B Farris; David M Guidot; Michael Koval; Mandy L Ford; Craig M Coopersmith Journal: PLoS One Date: 2013-05-22 Impact factor: 3.240