Complement depletion with cobra venom factor delays acute cell-mediated rejection in pig-to-mouse corneal xenotransplantation.
BACKGROUND
We have demonstrated earlier that porcine corneal xenografts underwent an acute cell-mediated rejection in mice despite the absence of T cells. In the present study, we investigated the effect of complement depletion by cobra venom factor (CVF) on the corneal xenograft rejection in a pig-to-mouse model.


METHODS
Porcine corneas were orthotopically transplanted into C57BL/6 (B6) and severe combined immunodeficiency (SCID) mice. For complement depletion, 25 microg of CVF (1 g/kg bodyweight) was injected intraperitoneally on the day before and 1, 3, 5, and 7 days after transplantation. Graft survival was clinically assessed by slit lamp biomicroscopy and the median survival time (MST) was calculated. The grafts were histologically evaluated serially after transplantation using antibodies against CD4, CD8, NK1.1, and F4/80.


RESULTS
The CVF treatment significantly prolonged the porcine corneal xenograft survival in both B6 (MST 9.4 vs. 15.5 days; P = 0.0011) and SCID mice (MST 16.4 vs. 20.5 days; P = 0.0474). Histologically, whereas macrophages and CD4(+) T cells were progressively infiltrated into porcine corneal grafts in CVF-untreated B6 mice, the infiltration by both cells was markedly delayed and decreased in the xenografts in CVF-treated B6 mice. Likewise, macrophage infiltration, which was prominent in rejected porcine xenografts in SCID mice, was also reduced in CVF-treated SCID mice.


CONCLUSIONS
Our results suggest that complement depletion by CVF delayed, although did not prevent, an acute cell-mediated rejection in a pig-to-mouse corneal xenotransplantation.
Seoul Artificial Eye Center, Seoul National University Hospital Clinical Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Joo Youn
JY
Oh
Mee Kum
MK
Kim
Hyun Ju
HJ
Lee
Jung Hwa
JH
Ko
Youngji
Y
Kim
Chan-Sik
CS
Park
Hee Jung
HJ
Kang
Chung-Gyu
CG
Park
Sang Joon
SJ
Kim
Jin Hak
JH
Lee
Won Ryang
WR
Wee
D000818:Animals; D003165:Complement System Proteins / Q000187:drug effects* / Q000276:immunology; D016039:Corneal Transplantation; D004546:Elapid Venoms / Q000494:pharmacology*; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology
D004546:Elapid Venoms; D003165:Complement System Proteins