title: Anti-endotoxin monoclonal antibodies are protective against hepatic ischemia/reperfusion injury in steatotic mice.
abstract: Steatotic mice are particularly susceptible to hepatic ischemia/reperfusion injury compared with their lean littermates. We have previously demonstrated that livers of mice having a spontaneous mutation in the leptin gene (ob/ob), resulting in global obesity and liver steatosis, are ATP depleted, are endotoxin sensitive, and do not survive (I/R) injury. We hypothesize that administration of an anti-LPS monoclonal antibody (mAb) prior to initiation of I/R would be protective from that insult. Steatotic mice (ob/ob) were subjected to 15 min of ischemia via complete porta-hepatis occlusion and varying lengths of reperfusion with or without pre-treatment with an anti-LPS mAb. There was 14-31% survival of isotype matched control mAb treated ob/ob mice after 15 min of ischemia and 24 h of reperfusion. In contrast, 75-83% of ob/ob mice pre-treated with an anti-LPS mAb prior to initiation of I/R survived both ischemia and 24 h of reperfusion. Furthermore, there was a decrease in ALT and circulating endotoxin levels when treated with an anti-LPS mAb compared with control antibodies. Attenuation of the endotoxin load with anti-LPS mAb, prior to initiation of I/R, was cytoprotective and improved survival. Consequently, these studies might offer a solution to the problems associated with using steatotic livers in clinical transplantation.
authors.affiliation: Department of Surgery, Division of Transplant, Medical University of South Carolina (MUSC), Charleston, SC, USA.
authors.forename: Ryan N
authors.initials: RN
authors.lastname: Fiorini
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Shafizadeh
authors.forename: Carmen
authors.initials: C
authors.lastname: Polito
authors.forename: David W
authors.initials: DW
authors.lastname: Rodwell
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.forename: Zachary
authors.initials: Z
authors.lastname: Evans
authors.forename: Chidan
authors.initials: C
authors.lastname: Wan
authors.forename: Sarah
authors.initials: S
authors.lastname: Belden
authors.forename: Julia K
authors.initials: JK
authors.lastname: Haines
authors.forename: Jennifer
authors.initials: J
authors.lastname: Birsner
authors.forename: David
authors.initials: D
authors.lastname: Lewin
authors.forename: Karen R
authors.initials: KR
authors.lastname: Wasiluk
authors.forename: David L
authors.initials: DL
authors.lastname: Dunn
authors.forename: Michael G
authors.initials: MG
authors.lastname: Schmidt
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Chavin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology / Q000502:physiology; D004731:Endotoxins / Q000097:blood / Q000276:immunology*; D005234:Fatty Liver; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D015427:Reperfusion Injury / Q000276:immunology / Q000517:prevention & control*
chemical_list: D000911:Antibodies, Monoclonal; D004731:Endotoxins