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Variation in the level of xenoantigen expression in porcine organs.

Publication ,  Journal Article
Alvarado, CG; Cotterell, AH; McCurry, KR; Collins, BH; Magee, JC; Berthold, J; Logan, JS; Platt, JL
Published in: Transplantation
June 15, 1995

Hyperacute rejection of vascularized porcine to primate xenografts is initiated by the binding of xenoreactive natural antibodies to donor endothelium. We tested the hypothesis that the level of xenoantigen expression varies in the population of potential porcine donors and may determine the amount of binding of xenoreactive natural antibodies to a porcine organ perfused by xenogeneic blood. Two hundred ninety pigs were studied using an inhibition ELISA that quantitated the xenoantigen level on porcine platelets. Based on this assay, the levels of xenoantigen expression in the population adhered to a normal distribution. Kidneys from pigs found to express high antigen levels and kidneys from pigs found to express low antigen levels were perfused with baboon blood using an extracorporeal circuit. In multiple experiments, a significant difference was observed in the amount of xenoreactive natural antibody adsorbed by high antigen versus low antigen organs. Normalizing for the weight of the perfused organs and for levels of natural antibody in individual baboons, high antigen organs adsorbed 3.6 +/- 1.3 U of xenoreactive natural antibody/g and low antigen organs adsorbed -0.8 +/- 1.0 U of xenoreactive natural antibody/g (P < 0.002). Immunopathology of tissues from the perfused organs demonstrated more deposition of IgM and C4 in high than in low xenoantigen organs. The quantitative relationship between binding of xenoreactive natural antibodies to platelets and to whole organs suggests that platelets are a valid representation of endothelial cell antigen expression in vivo. Despite the probable importance of Gal alpha(1-3)Gal as an epitope recognized by xenoreactive natural antibodies, differences in the binding to platelets or to organs of the GS-I-B4 lectin that recognizes that sugar had no correlation with the differences in binding of IgM to these tissues. Variation in expression of xenoantigen may be exploited to selectively breed donors for xenotransplantation that are less susceptible to attack by xenoreactive natural antibodies.

Duke Scholars

Published In

Transplantation

ISSN

0041-1337

Publication Date

June 15, 1995

Volume

59

Issue

11

Start / End Page

1589 / 1596

Location

United States

Related Subject Headings

  • Swine
  • Surgery
  • Gene Expression
  • Fluorescent Antibody Technique
  • Flow Cytometry
  • Enzyme-Linked Immunosorbent Assay
  • Endothelium
  • Cells, Cultured
  • Blood Platelets
  • Antigens, Heterophile
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Alvarado, C. G., Cotterell, A. H., McCurry, K. R., Collins, B. H., Magee, J. C., Berthold, J., … Platt, J. L. (1995). Variation in the level of xenoantigen expression in porcine organs. Transplantation, 59(11), 1589–1596.
Alvarado, C. G., A. H. Cotterell, K. R. McCurry, B. H. Collins, J. C. Magee, J. Berthold, J. S. Logan, and J. L. Platt. “Variation in the level of xenoantigen expression in porcine organs.Transplantation 59, no. 11 (June 15, 1995): 1589–96.
Alvarado CG, Cotterell AH, McCurry KR, Collins BH, Magee JC, Berthold J, et al. Variation in the level of xenoantigen expression in porcine organs. Transplantation. 1995 Jun 15;59(11):1589–96.
Alvarado, C. G., et al. “Variation in the level of xenoantigen expression in porcine organs.Transplantation, vol. 59, no. 11, June 1995, pp. 1589–96.
Alvarado CG, Cotterell AH, McCurry KR, Collins BH, Magee JC, Berthold J, Logan JS, Platt JL. Variation in the level of xenoantigen expression in porcine organs. Transplantation. 1995 Jun 15;59(11):1589–1596.

Published In

Transplantation

ISSN

0041-1337

Publication Date

June 15, 1995

Volume

59

Issue

11

Start / End Page

1589 / 1596

Location

United States

Related Subject Headings

  • Swine
  • Surgery
  • Gene Expression
  • Fluorescent Antibody Technique
  • Flow Cytometry
  • Enzyme-Linked Immunosorbent Assay
  • Endothelium
  • Cells, Cultured
  • Blood Platelets
  • Antigens, Heterophile