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.
Similar content being viewed by others
References
Armulik, A., Abramsson, A., Betsholtz, C., 2005. Endothelial/pericyte interactions. Circ. Res., 97(6):512–523. [doi:10.1161/01.RES.0000182903.16652.d7]
Beck, S., Barrell, B.G., 1988. Human cytomegalovirus encodes a glycoprotein homologous to MHC class I antigen. Nature, 331(6153):269–276. [doi:10.1038/331269a0]
Brennan, D.C., 2001. Cytomegalovirus in renal transplantation. J. Am. Soc. Nephrol., 12(1):848–855.
Cainelli, F., Vento, S., 2002. Infections and solid organ transplant rejection: a cause-and-effect relationship? Lancet Infect. Dis., 2(9):539–549. [doi:10.1016/S1473-3099(02)00370-5]
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.
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. [doi:10.1002/(SICI)1096-9071(200003)60:3〈313::AID-JMV10〉3.0.CO;2-K]
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.
Game, D.S., Warrens, A.N., Lechler, R.I., 2001. Rejection mechanisms in transplantation. Wien. Klin. Wochenschr., 113(20):832–838.
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. [doi:10.1016/j.humimm.2004.12.005]
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. [doi:10.1097/00007890-199111000-00027]
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. [doi:10.1111/j.1600-065X.1990.tb00568.x]
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. [doi:10.1097/00007890-199912270-00011]
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. [doi:10.1631/jzus.B0810188]
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. [doi:10.1097/00007890-198911000-00001]
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. [doi:10.1097/00007890-200006270-00026]
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. [doi:10.1097/00007890-199912150-00030]
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. [doi:10.1097/00007890-200002150-00019]
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. [doi:10.1016/j.trim.2007.07.004]
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. [doi:10.1152/ajpcell.00620.2004]
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. [doi:10.1159/000053961]
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. [doi:10.1021/jm00359a023]
Patel, R., Paya, C.V., 1997. Infections in solid-organ transplant recipients. Clin. Microbiol. Rev., 10(1):86–124.
Pober, J.S., Cotran, R.S., 1990. Cytokines and endothelial cell biology. Physiol. Rev., 70(2):427–451.
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. [doi:10.1016/S0140-6736(94)92887-8]
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.
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. [doi:10.1034/j.1600-6143.2002.20907.x]
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. [doi:10.1097/00007890-199002000-00043]
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. [doi:10.1099/0022-1317-76-4-741]
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. [doi:10.1111/j.1744-313X.2007.00727.x]
Tammela, T., Enholm, B., Alitalo, K., Paavonen, K., 2005. The biology of vascular endothelial growth factors. Cardiovasc. Res., 65(3):550–563. [doi:10.1016/j.cardiores.2004.12.002]
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. [doi:10.1097/00007890-200208270-00026]
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. [doi:10.1111/j.1432-2277.2000.tb01019.x]
Ustinov, J., Bruggeman, C., Hayry, P., Lautenschlager, I., 1994. Cytomegalovirus-induced class II expression in rat kidney. Transplant. Proc., 26(3):1729–1736.
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. [doi:10.1182/blood-2003-09-3296]
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. [doi:10.1097/00007890-198610000-00006]
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. [doi:10.1089/vim.2000.13.37]
Wyrwicz, L.S., Rychlewski, L., 2008. Cytomegalovirus immediate early gene UL37 encodes a novel MHC-like protein. Acta Biochim. Pol., 55(1):67–73.
Author information
Authors and Affiliations
Corresponding author
Additional information
The two authors contributed equally to this work
Project supported by the National Natural Science Foundation of China (No. 30772096), the Clinical Key Disciplines of National Public Health Department, the Major Scientific and Technological Special Projects of Shannxi Province (No. 2007ZDKG-67), and the Natural Science Foundation of Shaanxi Province (No. 30571799), China
Rights and permissions
About this article
Cite this article
Li, Y., Yan, H., Xue, Wj. et al. Allograft rejection-related gene expression in the endothelial cells of renal transplantation recipients after cytomegalovirus infection. J. Zhejiang Univ. Sci. B 10, 820–828 (2009). https://doi.org/10.1631/jzus.B0920115
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1631/jzus.B0920115
Key words
- Renal transplantation
- Cytomegalovirus (CMV)
- Rejection
- Intercellular adhesion molecule-1 (ICAM-1)
- Major histocompability complex (MHC)