Local and remote ischemia-reperfusion injury is mitigated in mice overexpressing human C1 inhibitor.
Activation of the classical complement pathway is crucially involved in complement-mediated endothelial cell damage in ischemia-reperfusion injury. C1 inhibitor is the only known physiological inhibitor of classical complement pathway activation. Transgenic mice overexpressing human C1 inhibitor were used in a surgical lower torso and a liver ischemia-reperfusion model. Organ-specific endothelial disruption was determined by 125I-tagged albumin extravasation. In the lower torso ischemia-reperfusion model, transgenic mice overexpressing the C1 inhibitor were protected in the muscle and the lungs from endothelial cell damage. In the liver ischemia-reperfusion model, endothelial cell integrity was preserved in transgenic animals in the liver, the gut and the lungs. Our data indicate that inhibiting complement activation by a transgenic approach is effective in protection against ischemia-reperfusion injury.
Inderbitzin
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Department of Visceral and Transplant Surgery, University Hospital Bern, Bern, Switzerland. daniel.inderbitzin@insel.ch
Beldi
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Avital
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I
Vinci
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Candinas
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D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D002199:Capillary Permeability; D003174:Complement C1 Inactivator Proteins / Q000235:genetics / Q000502:physiology*; D003171:Complement Pathway, Classical; D004730:Endothelium, Vascular / Q000293:injuries / Q000503:physiopathology; D015870:Gene Expression; D006801:Humans; D007457:Iodine Radioisotopes; D008099:Liver / Q000098:blood supply / Q000293:injuries; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control*
D000418:Albumins; D003174:Complement C1 Inactivator Proteins; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins