PMID- 22750067 OWN - NLM STAT- MEDLINE DCOM- 20121030 LR - 20211021 IS - 1872-9142 (Electronic) IS - 0161-5890 (Print) IS - 0161-5890 (Linking) VI - 52 IP - 3-4 DP - 2012 Oct TI - Human beta2-glycoprotein I attenuates mouse intestinal ischemia/reperfusion induced injury and inflammation. PG - 207-16 LID - 10.1016/j.molimm.2012.05.018 [doi] AB - Intestinal ischemia-reperfusion (IR)-induced injury results from a complex cascade of inflammatory components. In the mouse model of intestinal IR, the serum protein, beta2-glycoprotein I (beta2-GPI) binds to the cell surface early in the cascade. The bound beta2-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 beta2-GPI would alter IR-induced tissue injury. Administration of human but not mouse beta2-GPI attenuated IR-induced tissue damage and prostaglandin E(2) production indicating a physiological difference between beta2-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 beta2-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 beta2-GPI and attenuated IR-induced injury. We conclude that caution should be exercised in interpreting results obtained by using human beta2-GPI in a mouse model. CI - Copyright (c) 2012 Elsevier Ltd. All rights reserved. FAU - Tomasi, Maurizio AU - Tomasi M AD - Division of Biology, Kansas State University, Manhattan, KS 66506, United States. FAU - Hiromasa, Yasuaki AU - Hiromasa Y FAU - Pope, Michael R AU - Pope MR FAU - Gudlur, Sushanth AU - Gudlur S FAU - Tomich, John M AU - Tomich JM FAU - Fleming, Sherry D AU - Fleming SD LA - eng GR - P20 RR017686/RR/NCRR NIH HHS/United States GR - RR016475/RR/NCRR NIH HHS/United States GR - AI061691/AI/NIAID NIH HHS/United States GR - P20 RR016475/RR/NCRR NIH HHS/United States GR - R01 AI061691/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20120627 PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (Homeodomain Proteins) RN - 0 (beta 2-Glycoprotein I) RN - 128559-51-3 (RAG-1 protein) RN - K7Q1JQR04M (Dinoprostone) SB - IM MH - Amino Acid Sequence MH - Animals MH - Cell Membrane/metabolism MH - Dinoprostone/biosynthesis MH - Homeodomain Proteins/genetics MH - Humans MH - Inflammation/*immunology MH - Intestines/*immunology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Protein Structure, Secondary MH - Proteomics MH - Reperfusion Injury/drug therapy/*immunology MH - Sequence Alignment MH - beta 2-Glycoprotein I/*chemistry/*immunology/metabolism PMC - PMC3565431 MID - NIHMS384365 EDAT- 2012/07/04 06:00 MHDA- 2012/10/31 06:00 PMCR- 2013/10/01 CRDT- 2012/07/04 06:00 PHST- 2012/02/20 00:00 [received] PHST- 2012/05/23 00:00 [revised] PHST- 2012/05/31 00:00 [accepted] PHST- 2012/07/04 06:00 [entrez] PHST- 2012/07/04 06:00 [pubmed] PHST- 2012/10/31 06:00 [medline] PHST- 2013/10/01 00:00 [pmc-release] AID - S0161-5890(12)00319-7 [pii] AID - 10.1016/j.molimm.2012.05.018 [doi] PST - ppublish SO - Mol Immunol. 2012 Oct;52(3-4):207-16. doi: 10.1016/j.molimm.2012.05.018. Epub 2012 Jun 27.