title: Small β2-glycoprotein I peptides protect from intestinal ischemia reperfusion injury.
abstract: Intestinal ischemic events, which are followed by reperfusion, induce significant tissue damage and frequently result in multiple organ failure, with >70% mortality. Upon reperfusion, excessive inflammation leads to exacerbated tissue damage. Previous studies indicated that binding of the serum protein, β2-glycoprotein I, to the endothelium initiates a cascade of inflammatory molecules that is required for damage. We hypothesized that peptides derived from the binding domain (domain V) of β2-glycoprotein I would attenuate ischemia/reperfusion-induced damage and inflammation in a therapeutic manner. Using a mouse model of intestinal ischemia/reperfusion, we administered peptides either prior to ischemia or at clinically relevant time points during reperfusion and evaluated intestinal tissue damage and inflammation after 2 h of reperfusion. We demonstrate that multiple peptides attenuate injury and inflammation in a dose-dependent manner and, perhaps more significantly, are efficacious when administered up to 30 min after the onset of reperfusion. In addition, an all D-amino acid retro-inverso peptide was biologically active. Thus, the β2-glycoprotein I-derived peptides attenuate injury and inflammation when administered in a therapeutic manner in intestinal ischemia/reperfusion injury.
authors.affiliation: Division of Biology, Kansas State University, Manhattan, KS 66506, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Pope
authors.forename: Urska
authors.initials: U
authors.lastname: Bukovnik
authors.forename: John M
authors.initials: JM
authors.lastname: Tomich
authors.forename: Sherry D
authors.initials: SD
authors.lastname: Fleming
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D007422:Intestines / Q000276:immunology* / Q000473:pathology; D051379:Mice; D010455:Peptides / Q000276:immunology / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D053482:beta 2-Glycoprotein I / Q000276:immunology / Q000494:pharmacology*
chemical_list: D010455:Peptides; D053482:beta 2-Glycoprotein I