Human complement regulatory proteins protect swine lungs from xenogeneic injury

Mark Yeatman, C. William Daggett, Christine L. Lau, Guerard W. Byrne, John S. Logan, Jeffrey L. Platt, R. Duane Davis

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Background. Pulmonary xenotransplantation is not possible because of hyperacute lung injury, the pathogenesis of which is unknown. This study evaluates complement-dependent pathways of pulmonary injury during heterologous perfusion of swine lungs. Methods. Lungs from unmodified swine and swine expressing human decay-accelerating factor and human CD59 (hDAF/hCD59 swine) were perfused with either human plasma or baboon blood. Pulmonary vascular resistance and static pulmonary compliance were measured serially, and swine lung tissue were examined by light microscopy. Complement activation was assessed by serial measurements of baboon plasma C3a-desArg concentrations. Results. Perfusion of unmodified swine lungs with human plasma and baboon blood resulted in hyperacute lung injury within minutes of perfusion. However, function was preserved in swine lungs expressing human decay-accelerating factor and human CD59. In both study groups, xenogeneic perfusion with baboon blood resulted in at least a sevenfold increase in plasma C3a-desArg levels suggesting transient activation of complement. Conclusions. Lungs from swine expressing human decay-accelerating factor and human CD59 were resistant to injury during perfusion with human plasma and baboon blood, indicating that complement mediated some of the features of xenogeneic acute lung injury.

Original languageEnglish (US)
Pages (from-to)769-775
Number of pages7
JournalAnnals of Thoracic Surgery
Volume67
Issue number3
DOIs
StatePublished - Mar 1999
Externally publishedYes

Bibliographical note

Funding Information:
We acknowledge the assistance of the following people: Andrew J. Lodge, MD, Edward P. Chen, MD, Ronnie L. Johnson, Kurt A. Campbell, and George Quick for expert technical assistance. This work was supported in part by grants HL50985 and H152297 from the National Institutes of Health and from Nextran, Princeton, New Jersey.

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