Vaccinia virus complement control protein inhibits hyperacute xenorejection in a guinea pig-to-rat heterotopic cervical cardiac xenograft model by blocking both xenoantibody binding and complement pathway activation.
Vaccinia virus complement control protein (VCP) binds the activated third and fourth complement components and inhibits both alternative and classical pathways of activation. The ability of VCP to bind heparan sulfate allows the protein to attach itself to the cell surface, enabling it with many additional activities. Altogether, the many functions of VCP have been shown to suppress the inflammatory response of the host, helping the vaccinia virus to evade immune destruction. VCP has recently been shown to inhibit human anti-Gal alpha1-3 Gal antibody attachment to cultured porcine endothelial cells and reduce human neutrophil and NK killing of pig aortic endothelial cells through its ability to bind heparan sulfate. Here we demonstrate that in an in vivo guinea pig-to-rat heterotopic cervical cardiac xenograft model, recombinant VCP (rVCP) is able to block hyperacute xenograft rejection, significantly prolonging graft survival. Histopathological examination of transplanted hearts from rats receiving rVCP revealed a significant reduction in cardiac tissue damage as compared to control hearts. Finally, rVCP treated recipients demonstrated marked rVCP deposition on the endothelium and significantly less C3, IgG and IgM deposition in the tissue. rVCP is therefore able to inhibit hyperacute xenorejection by binding the endothelial surface, blocking complement fixation and activation, and preventing xenoantibody attachment.
Anderson
Jaime B
JB
Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY, USA.
Smith
Scott A
SA
van Wijk
Rochelle
R
Chien
Sufan
S
Kotwal
Girish J
GJ
D000818:Animals; D000910:Antibodies, Heterophile / Q000187:drug effects / Q000378:metabolism; D003167:Complement Activation / Q000187:drug effects* / Q000502:physiology; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006168:Guinea Pigs; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D014183:Transplantation, Heterologous; D014764:Viral Proteins / Q000494:pharmacology*
D000910:Antibodies, Heterophile; D011994:Recombinant Proteins; D014764:Viral Proteins; C066459:complement-control protein, Vaccinia virus