Premium
The Role of Antibodies and Von Willebrand Factor in Discordant Pulmonary Xenotransplantation
Author(s) -
Lau Christine L.,
Cantu Edward,
GonzalezStawinski Gonzalo V.,
Holzknecht Zoie E.,
Nichols Timothy C.,
Posther Katherine E.,
Rayborn Cory A.,
Platt Jeffrey L.,
Parker William,
Davis R. Duane
Publication year - 2003
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1034/j.1600-6143.2003.00190.x
Subject(s) - von willebrand factor , xenotransplantation , medicine , lung , immunology , transplantation , platelet , pathogenesis , antibody , endothelium , lung transplantation , pulmonary edema , pathology
Pulmonary xenotransplantation is one potential solution to the paucity of donors but is currently limited by rapid failure of the graft. Unlike cardiac and renal xenotransplants, pulmonary xenografts release large quantities of swine von Willebrand factor (vWF). Swine vWF binds xenoreactive antibodies and is capable of activating primate platelets. The contribution of swine vWF to lung xenograft dysfunction is not entirely clear. To probe the role vWF plays in xenograft dysfunction, we traced the fate of xenoantibodies in vWF+ and von Willebrand factor‐deficient (vWFD) swine lungs. These studies showed that the vast majority of xenoantibodies bind the vWF released from the vWF+ swine lung, and thus do not remain bound on lung endothelium. The vWF complexed to xenoantibody remained capable of aggregating primate platelets. With this information, we performed swine‐to‐baboon lung transplants using vWF+ and vWFD donors. Without vWF present to complex xenoantibodies, a picture of hyperacute rejection more typical of heart and kidney xenografts, with antibody deposition along the graft endothelium, interstitial hemorrhage, and edema occurred. These findings suggest that porcine vWF plays a major role in the pathogenesis of pulmonary xenograft dysfunction, and suggests promising strategies to treat lung xenograft dysfunction.