Human β2-glycoprotein I attenuates mouse intestinal ischemia/reperfusion induced injury and inflammation

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dc.contributor.author Tomasi, Maurizio
dc.contributor.author Hiromasa, Yasuaki
dc.contributor.author Pope, Michael R.
dc.contributor.author Gudlur, Sushanth
dc.contributor.author Tomich, John M.
dc.contributor.author Fleming, Sherry D.
dc.date.accessioned 2013-10-16T15:49:06Z
dc.date.available 2013-10-16T15:49:06Z
dc.date.issued 2013-10-16
dc.identifier.uri http://hdl.handle.net/2097/16671
dc.description.abstract Intestinal ischemia-reperfusion (IR)-induced injury results from a complex cascade of inflammatory components. In the mouse model of intestinal IR, the serum protein, β2-glycoprotein I (β2-GPI) binds to the cell surface early in the cascade. The bound β2-GPI undergoes a conformational change which exposes a neoantigen recognized by naturally occurring antibodies and initiates the complement cascade. We hypothesized that providing additional antigen with exogenous β2-GPI would alter IR-induced tissue injury. Administration of human but not mouse β2-GPI attenuated IR-induced tissue damage and prostaglandin E[subscript 2] production indicating a physiological difference between β2-GPI isolated from the two species. To investigate whether structural features were responsible for this physiological difference, we compared the chemical, physical and biochemical properties of the two proteins. Despite possessing 76% amino acid identity and 86% sequence homology, we found that mouse β2-GPI differs from the human protein in size, carbohydrate chain location, heterogeneity and secondary structural content. These data suggest that the structural differences result in mouse Ab recognition of soluble human but not mouse β2-GPI and attenuated IR-induced injury. We conclude that caution should be exercised in interpreting results obtained by using human β2-GPI in a mouse model. en_US
dc.language.iso en_US en_US
dc.relation.uri http://www.sciencedirect.com/science/article/pii/S0161589012003197 en_US
dc.subject Apolipoprotein H en_US
dc.subject Prostaglandin E2 en_US
dc.subject Mouse en_US
dc.subject Ischemia en_US
dc.title Human β2-glycoprotein I attenuates mouse intestinal ischemia/reperfusion induced injury and inflammation en_US
dc.type Article (author version) en_US
dc.date.published 2012 en_US
dc.citation.doi doi:10.1016/j.molimm.2012.05.018 en_US
dc.citation.epage 216 en_US
dc.citation.issue 3-4 en_US
dc.citation.jtitle Molecular Immunology en_US
dc.citation.spage 207 en_US
dc.citation.volume 52 en_US
dc.contributor.authoreid hiromasa en_US
dc.contributor.authoreid mpope en_US
dc.contributor.authoreid jtomich en_US
dc.contributor.authoreid sdflemin en_US


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