Complement-mediated pulmonary xenograft injury: Studies in swine-to- primate orthotopic single lung transplant models

Mark Yeatman, Casey W. Daggett, William Parker, Guerard W. Byrne, John S. Logan, Jeffrey L. Platt, R. Duane Davis

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Background. The pathogenesis of acute pulmonary xenograft injury has not yet been determined. The present study evaluates the role of complement in mediating pulmonary xenograft dysfunction by using cobra venom factor (CVF) to deplete recipient complement and transgenic swine, which express human regulators of complement activation (human decay-accelerating factor [hDAF] and hCD59). Methods. Fifteen orthotopic lung transplants were performed as follows: group I, swine-to-swine (n=5); group II, unmodified swine-to-baboon (n=3); group III, unmodified swine-to-(CVF treated) baboon (n=3); and group IV, hCD59/hDAF swine-to-baboon (n=4). Left pulmonary artery flow and pulmonary vascular resistance were measured at 30-min intervals. Serial lung biopsies were examined by light microscopy and immunofluorescence. The activation of complement was quantified by measurement of baboon plasma CH50 and C4 functional activity. Results. Group II xenotransplants ceased functioning within 30 min of reperfusion. Histopathologic abnormalities included erythrocyte/platelet aggregates and hemorrhagic pulmonary edema. Groups I and IV showed excellent function throughout. hDAF/hCD59 lungs (group IV) showed trace venular fibrin plugs and moderate loss of alveolar architecture. Pretreatment with CVF (group III) was infective in preventing xenograft injury. Conclusions. These results characterize the fundamental features of discordant pulmonary xenotransplantation. Correction of the known defects in the regulation of heterologous complement activation was partially effective in preventing pulmonary xenograft dysfunction, suggesting that complement mediates, in part, some of the features of acute lung injury after discordant lung xenotransplantation.

Original languageEnglish (US)
Pages (from-to)1084-1093
Number of pages10
JournalTransplantation
Volume65
Issue number8
DOIs
StatePublished - Apr 27 1998
Externally publishedYes

Fingerprint Dive into the research topics of 'Complement-mediated pulmonary xenograft injury: Studies in swine-to- primate orthotopic single lung transplant models'. Together they form a unique fingerprint.

Cite this