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J Surg Res ; 203(1): 15-21, 2016 06 01.
Article in English | MEDLINE | ID: mdl-27338529

ABSTRACT

BACKGROUND: Hypodermin A (HA) is a serine esterase that degrades complement, a key element of the innate immune system. Immunosuppressive properties of HA have previously been studied in vitro. However, such properties have not been fully demonstrated in vivo. The aim of this study was to evaluate the effect of HA in inhibiting allograft rejection in an HA transgenic mouse model. METHODS: FVB (HA transgenic mice or wild-type mice) to BALB/c mice skin transplantation model were used. Skin grafts were analyzed by histology, immunohistochemistry, and Western blotting. RESULTS: HA overexpression resulted in significantly prolonged skin allograft survival. Histologic changes in the skin allografts paralleled the gross appearance of rejection. ELISA and Western blotting showed that HA significantly reduced the content of complement C3 and C9 in HA skin allografts. The expressions of CD4, B7-2, and MHC class II were all significantly suppressed in HA skin allografts compared with the control group. CONCLUSIONS: These findings suggest that HA effectively prolongs skin allograft survival. The study results provide insight into a promising strategy to improve the survival of grafts in humans.


Subject(s)
Genetic Therapy/methods , Graft Rejection/prevention & control , Graft Survival/immunology , Serine Endopeptidases/immunology , Skin Transplantation , Animals , Biomarkers/metabolism , Blotting, Western , Enzyme-Linked Immunosorbent Assay , Female , Graft Rejection/enzymology , Graft Rejection/genetics , Graft Rejection/immunology , Graft Survival/genetics , Immunohistochemistry , Mice , Mice, Inbred BALB C , Mice, Transgenic , Serine Endopeptidases/genetics , Serine Endopeptidases/metabolism , Transplantation, Homologous , Treatment Outcome , Up-Regulation
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