Immunosuppressive Effect of Hypodermin C on Complement Component 3 In Vitro
Tóm tắt
Hypodermins A (HA), B (HB) and C (HC) are the major proteases secreted by first-instar larvae of Hypoderma lineatum (Diptera: Oestridae). These proteases are involved in the larval migration in the tissue, and prevent the activation of the host immune response. We previously showed that the recombinant HA functions as an immunosuppressive agent which could inhibit the rejection of xenotransplants. In the current study, we cloned the cDNA sequence of HC, which was transfected in Cos7 cells using the pEF1α-IRES-AcGFP expression vector. The Cos7 cells stably expressed HC, and were more resistant to lysis by guinea pig C3 than the control cells. The HC protease degraded the guinea pig C3, and inhibited the complement pathway in vitro. The DNA binding sites of HC were identified using an electrophoretic mobility shift assay. Our findings suggest that the recombinant HC might be useful as an immunosuppressive agent for the inhibition of the xenotransplant rejection.
Tài liệu tham khảo
Vadori, M., & Cozzi, E. (2014). Immunological challenges and therapies in xenotransplantation. Cold Spring Harbor Perspectives in Medicine, 4(4), a015578.
Khan, M. A., & Nicolls, M. R. (2013). Complement-mediated microvascular injury leads to chronic rejection. In complement therapeutics (pp. 233–246). USA: Springer.
Pratt, J. R., Jones, M. E., Dong, J., Zhou, W., Chowdhury, P., Smith, R. A., & Sacks, S. H. (2003). Nontransgenic hyperexpression of a complement regulator in donor kidney modulates transplant ischemia/reperfusion damage, acute rejection, and chronic nephropathy. The American Journal of Pathology, 163(4), 1457–1465.
Malassagne, B., Regimbeau, J. M., Taboit, F., Troalen, F., Chereau, C., Moire, N., & Weill, B. (2003). Hypodermin A, a new inhibitor of human complement for the prevention of xenogeneic hyperacute rejection. Xenotransplantation, 10(3), 267–277.
Moiré, N., Bigot, Y., Periquet, G., & Boulard, C. (1994). Sequencing and gene expression of hypodermins A, B, C in larval stages of Hypoderma lineatum. Molecular and Biochemical Parasitology, 66(2), 233–240.
Panadero, R., Dacal, V., López, C., Vázquez, L., Cienfuegos, S., Díaz, P., & DÍEZ-BAÑOS, P. (2009). Immunomodulatory effect of Hypoderma lineatum antigens: in vitro effect on bovine lymphocyte proliferation and cytokine production. Parasite Immunology, 31(2), 72–77.
Moiré, N. (1998). Hypodermin A and inhibition of lymphocyte proliferation. Parasitology Today, 14(11), 455–457.
Sacks, S. H., & Zhou, W. (2012). The role of complement in the early immune response to transplantation. Nature Reviews Immunology, 12(6), 431–442.
Tagawa, T. (2011). Protease inhibitor nafamostat mesilate attenuates complement activation and improves function of xenografts in a discordant lung perfusion model. Xenotransplantation, 18(6), 315–319.
Kang, H. J., Lee, H., Ha, J. M., Lee, J. I., Shin, J. S., Kim, K. Y., & Kim, S. J. (2014). The role of the alternative complement pathway in early graft loss after intraportal porcine islet xenotransplantation. Transplantation, 97(10), 999–1008.
Baron, R. W. (1990). Cleavage of purified bovine complement component C3 in larval Hypoderma lineatum (Diptera: Oestridae) hypodermins. Journal of Medical Entomology, 27(5), 899–904.
Chen, R. J., Hu, A. K., Yuan, H. H., Wang, Z. Z., Ji, D. J., Wu, L. L., & Zhu, X. R. (2014). The immunosuppression mechanism of hypodermin A on complement. Parasitology International, 63(2), 392–396.
Chabaudie, N., & Boulard, C. (1992). Effect of hypodermin A, an enzyme secreted by Hypoderma lineatum(Insect Oestridae), on the bovine immune system. Veterinary Immunology and Immunopathology, 31(1), 167–177.
Moiré, N., Nicolas-Gaulard, I., Le Vern, Y., & Boulard, C. (1997). Enzymatic effect of hypodermin A, a parasite protease, on bovine lymphocyte membrane antigens. Parasite Immunology, 19(1), 21–27.
Sun, D., & Hurley, L.H. (2010) Biochemical techniques for the characterization of G-quadruplex structures: EMSA, DMS footprinting, and DNA polymerase stop assay. In G-Quadruplex DNA (pp. 65–79). Humana Press.
Boulard, C. (1989). Degradation of bovine C3 by serine proteases from parasites Hypoderma lineatum (Diptera, Oestridae). Veterinary Immunology and Immunopathology, 20(4), 387–398.