JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B 2009 Vol.10 No.11 P.820-828

http://doi.org/10.1631/jzus.B0920115

Allograft rejection-related gene expression in the endothelial cells of renal transplantation recipients after cytomegalovirus infection

Author(s): Yang LI, Hang YAN, Wu-jun XUE, Pu-xun TIAN, Xiao-ming DING, Xiao-ming PAN, Xin-shun FENG, Xiao-hui TIAN, He-li XIANG, Jun HOU
Affiliation(s): Department of Renal Transplantation, Center of Nephropathy, the First Affiliated Hospital, School of Medicine, Xi’ more
Corresponding email(s): jullian80915@126.com, yanhang2477@sina.com
Key Words: Renal transplantation, Cytomegalovirus (CMV), Rejection, Intercellular adhesion molecule-1 (ICAM-1), Major histocompability complex (MHC)

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Abstract: Objective: To explore the effects of cytomegalovirus (CMV) infection on rejection-related gene expression in the endothelial cells of renal transplantation recipients. Methods: Endothelial cells (ECs) were cultured and stimulated by a variety of factors: A, normal control group; B, inactivated human cytomegalovirus (HCMV) infection group; C, HCMV infection group; D, HCMV supernatant infection group; and E, ganciclovir HCMV group. Expression of intercellular adhesion molecule-1 (ICAM-1) and major histocompability complex (MHC) class I and class II antigens was detected by flow cytometry (FCM) and immunohistochemistry. Results: We found characteristic CMV-infected ECs in this study. There were no significant differences among groups A, B and D (P>0.05). Although the expression levels of ICAM-1 were not significantly different between groups C and E (P>0.05), the ICAM-1 expression in these two groups was significantly higher than that in group A (P<0.05). ICAM-1 expression was detected in groups C and E, while there was no expression in groups A, B and D. Furthermore, there was no significant difference of ICAM-1 mRNA expression between groups C and E (P>0.05). Human leucocyte antigen (HLA)-ABC expression was detected in all the groups, while HLA-DR expression was only detected in groups C and E. There were no significant differences of HLA-ABC and HLA-DR expression among groups A, B and D (P>0.05). However, the HLA-ABC and HLA-DR expression levels in groups C and D were higher than those of the remaining groups previously reported (P<0.05). Meanwhile, the HLA-ABC and HLA-DR expression levels in group E were lower than those of group C (P<0.05). Conclusion: CMV could up-regulate the expression levels of ICAM-1 and MHC antigens, which was closely related to allograft rejection.

Reference

[1] Armulik, A., Abramsson, A., Betsholtz, C., 2005. Endothelial/ pericyte interactions. Circ. Res., 97(6):512-523.

[2] Beck, S., Barrell, B.G., 1988. Human cytomegalovirus encodes a glycoprotein homologous to MHC class I antigen. Nature, 331(6153):269-276.

[3] Brennan, D.C., 2001. Cytomegalovirus in renal transplantation. J. Am. Soc. Nephrol., 12(1):848-855.

[4] Cainelli, F., Vento, S., 2002. Infections and solid organ transplant rejection: a cause-and-effect relationship? Lancet Infect. Dis., 2(9):539-549.

[5] Cheng, Y.C., Grill, S.P., Dutschman, G.E., Nakayamak, K., Bastow, K.F., 1983. Metabolism of 9-(1,3-dihydroxy-2-propoxymethyl) guanine, a new anti-herpes virus compound, in herpes simplex virus-infected cells. J. Biol. Chem., 258(20):12460-12664.

[6] Cinatl, J.Jr., Kotchekov, R., Weimer, E., Blaheta, R.A., Scholz, M., Vogel, J.U., Gumbel, H.O., Doerr, H.W., 2000. The antisense oligonucleotide ISIS 2922 prevents cytomegalovirus-induced upregulation of IL-8 and ICAM-1 in cultured human fibroblasts. J. Med. Virol., 60(3):313-323.

[7] Fujinami, R.S., Nelson, J.A., Walker, L., Oldstone, M.B., 1988. Sequence homology and immunologic cross-reactivity of human cytomegalovirus with HLA-DR chain: a means for graft rejection and immunosuppression. J. Virol., 62(1):100-105.

[8] Game, D.S., Warrens, A.N., Lechler, R.I., 2001. Rejection mechanisms in transplantation. Wien. Klin. Wochenschr., 113(20):832-838.

[9] Haynes, L.D., Waldman, W.J., Bushkin, Y., Love, R.B., Burlingham, W.J., 2005. CMV-infected allogeneic endothelial cells initiate responder and bystander donor HLA class I release via the metalloproteinase cleavage pathway. Hum. Immunol., 66(3):211-221.

[10] Hosenpud, J.D., Chou, S.W., Wagner, C.R., 1991. Cytomegalovirus-induced regulation of major histocompatibility complex class I antigen expression in human aortic smooth muscle cells. Transplantation, 52(5): 896-902.

[11] Hughes, C.C., Savage, C.O., Pober, J.S., 1990. The endothelial cell as a regulator of T cell function. Immunol. Rev., 117(1):85-102.

[12] Humar, A., Gillingham, K.J., Payne, W.D., Dunn, D.L., Sutherland, D.E.R., Matas, A.J., 1999. Association between cytomegalovirus disease and chronic rejection in kidney transplant recipients. Transplantation, 68(12): 1879-1885.

[13] Jiang, Y.F., Zhao, F.D., Li, X.B., Ning, Y.X., Zhi, X.L., Qian, R.Z., Yin, L.H., 2008. Effects of RNA interference-induced tryptase down-regulation in P815 cells on IL-6 and TNF-alpha release of endothelial cells. J. Zhejiang Univ. Sci. B, 9(8):656-661.

[14] Jutila, M.A., Berg, E.L., Kishimoto, T.K., Picker, L.J., Bargatze, R.F., Bishop, D.K., Orosz, C.G., Wu, N.W., Butcher, E.C., 1989. Inflammation-induced endothelial cell adhesion to lymphocytes, neutrophils, and monocytes. Role of homing receptors and other adhesion molecules. Transplantation, 48(5):727-731.

[15] Kloover, J.S., Soots, A.P., Krogerus, L.A., Kauppinen, H.O., Loginov, R.J., Holma, K.L., Bruggeman, C.A., Ahonen, P.J., Lautenschlager, I.T., 2000. Rat cytomegalovirus infection in kidney allograft recipients is associated with increased expression of intercellular adhesion molecule-1, vascular adhesion molecule-1, and their ligands leukocyte function antigen-1 and very late antigen-4 in the graft. Transplantation, 69(12):2641-3647.

[16] Knight, D.A., Waldman, W.J., Sedmak, D.D., 1999. Cytomegalovirus-mediated modulation of adhesion molecule expression by human arterial and microvascular endothelial cells. Transplantation, 68(11):1814-1818.

[17] Knight, D.A., Briggs, B.R., Bennett, C.R., Harindranath, N., Waldman, W.J., Sedmak, D.D., 2000. Attenuation of cytomegalovirus-induced endothelial intercellular adhesion molecule-1 mRNA/protein expression and T lymphocyte adhesion by a 2′-O-methoxyethyl antisense oligonucleotide. Transplantation, 69(3):417-426.

[18] Krogerus, L., Soots, A., Loginov, R., Bruggeman, C., Lautenschlager, I., 2008. CMV increases tubular apoptosis through the TNF-alpha-TNF-R1 pathway in a rat model of chronic renal allograft rejection. Transpl. Immunol., 18(3):232-236.

[19] Kuldo, J.M., Westra, J., Asgeirsdottir, S.A., Kok, R.J., Oosterhuis, K., Rots, M.G., Schouten, J.P., Limburg, P.C., Molema, G., 2005. Differential effects of NF-{kappa}B and p38 MAPK inhibitors and combinations thereof on TNF-{alpha}- and IL-1{beta}-induced proinflammatory status of endothelial cells in vitro. Am. J. Physiol. Cell Physiol., 289(5):C1229-C1239.

[20] Lautenschlager, I., Soots, A., Krogerus, L., Inkinen, K., Kloover, J., Loginov, R., Holma, K., Kauppinen, H., Bruggeman, C., Ahonen, J., 1999. Time-related effects of cytomegalovirus infection on the development of chronic renal allograft rejection in a rat model. Intervirology, 42(5-6):279-284.

[21] Martin, J.C., Dvorak, C.A., Smee, D.F., Matthews, T.R., Verheyden, J.P.H., 1983. 9-[(1,3-dihydroxy-2-propoxy) methyl]guanine: a new potent and selective antiherpes agent. J. Med. Chem., 26(5):759-761.

[22] Patel, R., Paya, C.V., 1997. Infections in solid-organ transplant recipients. Clin. Microbiol. Rev., 10(1):86-124.

[23] Pober, J.S., Cotran, R.S., 1990. Cytokines and endothelial cell biology. Physiol. Rev., 70(2):427-451.

[24] Reinke, P., Fietze, E., Odehakim, S., Prosch, S., Lippert, J., Ewert, R., Volk, H.D., 1994. Late acute renal allograft rejection and symptomless cytomegalovirus infection. Lancet, 344(8939-8940):1737-1738.

[25] Roberts, W.H., Sneddon, J.M., Waldman, W.J., Stephens, R.E., 1989. Cytomegalovirus infection of gastrointestinal endothelium demonstrated by simultaneous nucleic acid hybridization and immunohistochemistry. Arch. Pathol. Lab. Med., 113(5):461-464.

[26] Sagedal, S., Nordal, K.P., Hartmann, A., Sund, S., Scott, H., Degre, M., Foss, A., Leivestad, T., Osnes, K., Fauchald, P., Rollag, H., 2002. The impact of cytomegalovirus infection and disease on rejection episodes in renal allograft recipients. Am. J. Transplant., 2(9):850-856.

[27] Sedmak, D.D., Roberts, W.H., Stephens, R.E., Buesching, W.J., Morgan, L.A., Davis, D.H., Waldman, W.J., 1990. Inability of cytomegalovirus infection of cultured endothelial cells to induce HLA class II antigen expression. Transplantation, 49(2):458-462.

[28] Sinzger, C., Grefte, A., Plachter, B., Gouwash, A.S.H., The, T.H., Jahn, G., 1995. Fibroblasts, epithelial cells, endothelial cells and smooth muscle cells are major targets of human cytomegalovirus infection in lung and gastrointestinal tissues. J. Gen. Virol., 76(4):741-745.

[29] Tajik, N., Salari, F., Ghods, A.J., Hajilooi, M., Radjabzadeh, M.F., Mousavi, T., 2008. Association between recipient ICAM-1 K469 allele and renal allograft acute rejection. Int. J. Immunoqenet., 35(1):9-13.

[30] Tammela, T., Enholm, B., Alitalo, K., Paavonen, K., 2005. The biology of vascular endothelial growth factors. Cardiovasc. Res., 65(3):550-563.

[31] Tong, C.Y.W., Bakran, A., Peiris, J.S.M., Muir, P., Herrington, C.S., 2002. The association of viral infection and chronic allograft nephropathy with graft dysfunction after renal transplantation. Transplantation, 74(4):576-578.

[32] Toupance, O., Bouedjoro, M.C., Carquin, J., Carquin, J., Novella, J.L., Lavaud, S., Wynckel, A., Jolly, D., Chanard, J., 2000. Cytomegalovirus-related disease and risk of acute rejection in renal transplant recipients: a cohort study with case-control analyses. Transpl. Int., 13(6):413-419.

[33] Ustinov, J., Bruggeman, C., Hayry, P., Lautenschlager, I., 1994. Cytomegalovirus-induced class II expression in rat kidney. Transplant. Proc., 26(3):1729-1736.

[34] Viemann, D., Goebeler, M., Schmid, S., Klimmek, K., Sorg, C., Ludwig, S., Roth, J., 2004. Transcriptional profiling of IKK2/NF-kappa B- and p38 MAP kinase-dependent gene expression in TNF-alpha-stimulated primary human endothelial cells. Blood, 103(9):3365-3373.

[35] von Willebrand, E., Pettersson, E., Ahonen, J., Ahonen, J., Hayry, P., 1986. CMV infection, class-II antigen expression, and human kidney allograft-rejection. Transplantation, 42(4):364-367.

[36] Weinberg, A., Zhang, L., Hayward, A.R., 2000. Alloreactive cytotoxic CD4⁺ responses elicited by cytomegalovirus-infected endothelial cells: role of MHC class I antigens. Viral. Immunol., 13(1):37-47.

[37] Wyrwicz, L.S., Rychlewski, L., 2008. Cytomegalovirus immediate early gene UL37 encodes a novel MHC-like protein. Acta Biochim. Pol., 55(1):67-73.

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