TY - JOUR
T1 - Human β2-glycoprotein I attenuates mouse intestinal ischemia/reperfusion induced injury and inflammation
AU - Tomasi, Maurizio
AU - Hiromasa, Yasuaki
AU - Pope, Michael R.
AU - Gudlur, Sushanth
AU - Tomich, John M.
AU - Fleming, Sherry D.
N1 - Funding Information:
We would like to thank Mr. Andrew Fritze for technical assistance with immunohistochemistry and PGE 2 assays. This work was supported by NIH grant AI061691 (SDF) and P20 RR017686 (SDF), and RR016475 (SDF) from the Institutional Development Award Program of the National Center for Research Resources and the Johnson Center for Basic Cancer Research (SDF). Support for the project was also made possible in part by a KSU Targeted Excellence Award (JMT) and an NSF Major Research Instrumentation Program Grant No. 0521587 (JMT).
PY - 2012/10
Y1 - 2012/10
N2 - 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 E2 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.
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, 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 E2 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.
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U2 - 10.1016/j.molimm.2012.05.018
DO - 10.1016/j.molimm.2012.05.018
M3 - Article
C2 - 22750067
AN - SCOPUS:84862726553
SN - 0161-5890
VL - 52
SP - 207
EP - 216
JO - Molecular Immunology
JF - Molecular Immunology
IS - 3-4
ER -