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The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts.

Publication ,  Journal Article
Pruitt, SK; Kirk, AD; Bollinger, RR; Marsh, HC; Collins, BH; Levin, JL; Mault, JR; Heinle, JS; Ibrahim, S; Rudolph, AR
Published in: Transplantation
February 1994

The use of xenografts (Xgs) from distantly related species to relieve the increasing shortage of organs for clinical transplantation is prevented by the occurrence of hyperacute rejection (HAR). This process, in which C activation plays a central role, cannot be inhibited with currently available immunosuppressants. In two clinically relevant xenotransplantation models, this study evaluated the effect of C inhibition using recombinant soluble complement receptor type 1 (sCR1) on HAR. In an ex vivo model in which porcine cardiac Xgs were perfused with human blood, cardiac function ceased within 34 min when the perfusate blood was untreated (n = 3). When the perfusate blood was treated with sCR1 (300 micrograms/ml), cardiac Xg function was maintained for up to 4 hr (n = 3). Immunohistologic examination of these Xgs demonstrated deposition of C3b/iC3b and C3d in Xgs perfused with untreated human blood but only C3d deposition in those Xgs perfused with sCR1-treated human blood. These findings are consistent with the cofactor activity of sCR1 for factor I-mediated degradation of deposited C3b/iC3b to C3d. Treatment with sCR1 also prevented the histopathologic changes of HAR observed when untreated blood was used as the perfusate. In an in vivo pig-to-primate heterotopic cardiac xenotransplantation model, in which porcine Xgs transplanted into untreated cynomolgus monkey recipients underwent HAR in 1 hr or less (n = 3), a single intravenous bolus of sCR1 (15 mg/kg) administered to the recipient immediately before Xg reperfusion markedly inhibited total and alternative pathway serum C activity and prolonged Xg survival to between 48 and 90 hr (n = 5). These studies confirm the important role of C activation in HAR of porcine cardiac Xgs by primates and indicate that sCR1 may be a useful agent for xenotransplantation.

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Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

February 1994

Volume

57

Issue

3

Start / End Page

363 / 370

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Swine
  • Surgery
  • Receptors, Complement
  • Models, Biological
  • Microscopy, Fluorescence
  • Male
  • Humans
  • Heart Transplantation
  • Haplorhini
 

Citation

APA
Chicago
ICMJE
MLA
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Pruitt, S. K., Kirk, A. D., Bollinger, R. R., Marsh, H. C., Collins, B. H., Levin, J. L., … Rudolph, A. R. (1994). The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts. Transplantation, 57(3), 363–370. https://doi.org/10.1097/00007890-199402150-00009
Pruitt, S. K., A. D. Kirk, R. R. Bollinger, H. C. Marsh, B. H. Collins, J. L. Levin, J. R. Mault, J. S. Heinle, S. Ibrahim, and A. R. Rudolph. “The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts.Transplantation 57, no. 3 (February 1994): 363–70. https://doi.org/10.1097/00007890-199402150-00009.
Pruitt SK, Kirk AD, Bollinger RR, Marsh HC, Collins BH, Levin JL, et al. The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts. Transplantation. 1994 Feb;57(3):363–70.
Pruitt, S. K., et al. “The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts.Transplantation, vol. 57, no. 3, Feb. 1994, pp. 363–70. Pubmed, doi:10.1097/00007890-199402150-00009.
Pruitt SK, Kirk AD, Bollinger RR, Marsh HC, Collins BH, Levin JL, Mault JR, Heinle JS, Ibrahim S, Rudolph AR. The effect of soluble complement receptor type 1 on hyperacute rejection of porcine xenografts. Transplantation. 1994 Feb;57(3):363–370.

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

February 1994

Volume

57

Issue

3

Start / End Page

363 / 370

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Swine
  • Surgery
  • Receptors, Complement
  • Models, Biological
  • Microscopy, Fluorescence
  • Male
  • Humans
  • Heart Transplantation
  • Haplorhini