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Complement depletion with cobra venom factor delays acute cell‐mediated rejection in pig‐to‐mouse corneal xenotransplantation
Author(s) -
Oh Joo Youn,
Kim Mee Kum,
Lee Hyun Ju,
Ko Jung Hwa,
Kim Youngji,
Park ChanSik,
Kang Hee Jung,
Park ChungGyu,
Kim Sang Joon,
Lee Jin Hak,
Wee Won Ryang
Publication year - 2010
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/j.1399-3089.2010.00574.x
Subject(s) - xenotransplantation , cd8 , transplantation , complement system , immunology , medicine , andrology , corneal transplantation , immune system
Oh JY, Kim MK, Lee HJ, Ko JH, Kim Y, Park CS, Kang HJ, Park CG, Kim SJ, Lee JH, Wee WR. Complement depletion with cobra venom factor delays acute cell‐mediated rejection in pig‐to‐mouse corneal xenotransplantation. Xenotransplantation 2010; 17: 140–146. © 2010 John Wiley & Sons A/S. Abstract: 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 μ g 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.