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Hypodermin C improves the survival of kidney allografts
Affiliation:1. Laboratory Animal Center, Xuzhou Medical University, Xuzhou, Jiangsu, China;2. Department of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, China;3. Jiangsu Key Laboratory of Immunity and Metabolism, Laboratory of Infection and Immunity, Department of Pathogenic Biology and Immunology, Laboratory of Infection and Immunity, Xuzhou Medical University, Xuzhou, China;1. Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan;2. Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka, Japan;3. Department of General Surgery, The First Affiliated Hospital of Soochow University, China;4. AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan;5. Department of Pharmacy, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China;1. Victorian Transplantation and Immunogenetics Service, Australian Red Cross Blood Service, Melbourne, Australia;2. Lung Transplant Service, Alfred Hospital, Melbourne, Australia;3. Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection and Immunity, Melbourne, Australia;1. Department of Basic Medicine, Tianjin Medical College, Tianjin, China;2. School of Basic Medical Science, Tianjin Medical University, Tianjin, China;3. School of Medical Laboratory, Tianjin Medical University, Tianjin, China;1. Treatment and Research Center for Infectious Disease, 302 Military Hospital of China, Peking University Teaching Hospital, Beijing, China;2. Research Center for Liver transplantation, Beijing 302 Hospital, Beijing, China;3. Bengbu Medical College, Bengbu, Anhui, China;4. Treatment and Research Center for Infectious Disease, Beijing 302 Hospital, Beijing, China
Abstract:Although immunosuppressive therapies have made organ transplantation a common medical procedure worldwide, chronic toxicity is a major issue of long-term treatment. One method to improve such therapies is the application of immunomodulatory agents from parasites, such as Hypoderma lineatum (Diptera: Oestridae). Hypodermin C (HC) is an enzyme secreted by H. lineatum larvae, and our previous study showed that recombinant HC could degrade guinea pig C3 and inhibit the complement pathway in vitro, suggesting potential activity for inhibiting transplant rejection. However, such properties have not been fully demonstrated in vivo. In this study, we investigated the impact of HC on a fully MHC-mismatched, life-sustaining, murine model of kidney allograft rejection using B6 donors and BABL/c (HC transgenic or wild-type) recipients. Kidney grafts were analyzed by histology, immunohistochemistry and western blotting. The results suggested that HC could effectively inhibit kidney allograft rejection. These findings suggest HC is a promising strategy to improve the survival of human implants.
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