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Divergent pathogenesis and manifestations of hyperacute and acute vascular xenograft rejection

Publication ,  Conference
Lin, SS; Saadi, S; Kalady, MF; Busto, M; Parker, W; Davis, RD; Platt, JL
Published in: FASEB Journal
1998

A porcine heart transplanted in a human or non-human primate is subject to hyperacute rejection (HAR) which destroys the xenograft within minutes to hours after reperfusion. When HAR is averted, acute vascular rejection (AVR) typically occurs several days after transplantation and has been sometimes called "delayed xenograft rejection" because it was once thought to be a "delayed" form of HAR. To compare the pathogenesis of HAR and AVR, we systematically analyzed in transplanted pig-to-baboon cardiac xenografts the immune factors and pathological manifestations involved in these two processes. Both HAR and AVR were associated with deposition of IgM and were prevented by depletion of anti-donor antibodies. HAR but not AVR was prevented by partial inhibition of complement. Histopathologically, HAR was associated with interstitial hemorrhage, edema, and formation of platelet thrombi, while AVR was characterized by endothelial cell swelling, ischemia, and formation of fibrin thrombi. At the ultrastructural level, HAR was characterized by widespread platelet aggregation and AVR by activated endothelial cell morphology. Immunofluorescence studies in xenografts undergoing AVR revealed increased expression of plasminogen activator inhibitor-1 and E-selectin. These observations are consistent with the concept that the pathogenesis of HAR involves the loss of endothelial function, whereas that of AVR is associated with endothelial cell activation leading to acquisition of new, pathogenetic functions. Thus, HAR and AVR occur through distinct pathways.

Duke Scholars

Published In

FASEB Journal

ISSN

0892-6638

Publication Date

1998

Volume

12

Issue

4

Start / End Page

A488

Related Subject Headings

  • Biochemistry & Molecular Biology
  • 3208 Medical physiology
  • 3101 Biochemistry and cell biology
  • 1116 Medical Physiology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lin, S. S., Saadi, S., Kalady, M. F., Busto, M., Parker, W., Davis, R. D., & Platt, J. L. (1998). Divergent pathogenesis and manifestations of hyperacute and acute vascular xenograft rejection. In FASEB Journal (Vol. 12, p. A488).
Lin, S. S., S. Saadi, M. F. Kalady, M. Busto, W. Parker, R. D. Davis, and J. L. Platt. “Divergent pathogenesis and manifestations of hyperacute and acute vascular xenograft rejection.” In FASEB Journal, 12:A488, 1998.
Lin SS, Saadi S, Kalady MF, Busto M, Parker W, Davis RD, et al. Divergent pathogenesis and manifestations of hyperacute and acute vascular xenograft rejection. In: FASEB Journal. 1998. p. A488.
Lin, S. S., et al. “Divergent pathogenesis and manifestations of hyperacute and acute vascular xenograft rejection.” FASEB Journal, vol. 12, no. 4, 1998, p. A488.
Lin SS, Saadi S, Kalady MF, Busto M, Parker W, Davis RD, Platt JL. Divergent pathogenesis and manifestations of hyperacute and acute vascular xenograft rejection. FASEB Journal. 1998. p. A488.

Published In

FASEB Journal

ISSN

0892-6638

Publication Date

1998

Volume

12

Issue

4

Start / End Page

A488

Related Subject Headings

  • Biochemistry & Molecular Biology
  • 3208 Medical physiology
  • 3101 Biochemistry and cell biology
  • 1116 Medical Physiology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology