Cytomegalovirus-mediated upregulation of chemokine expression correlates with the acceleration of chronic rejection in rat heart transplants

被引:66
作者
Streblow, DN
Kreklywich, C
Yin, Q
De La Melena, VT
Corless, CL
Smith, PA
Brakebill, C
Cook, JW
Vink, C
Bruggeman, CA
Nelson, JA
Orloff, SL
机构
[1] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA
[2] Oregon Hlth & Sci Univ, Dept Mol Microbiol, Portland, OR 97201 USA
[3] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97201 USA
[4] Oregon Hlth & Sci Univ, Gene Therapy Inst, Portland, OR 97201 USA
[5] Portland VA Med Ctr, Portland, OR 97201 USA
[6] Univ Maastricht, Dept Microbiol, Maastricht, Netherlands
关键词
D O I
10.1128/JVI.77.3.2182-2194.2003
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Cytomegalovirus (CMV) infections have been shown to dramatically affect solid organ transplant graft survival in both human and animal models. Recently, it was demonstrated that rat CMV (RCMV) infection accelerates the development of transplant vascular sclerosis (TVS) in both rat heart and small bowel graft transplants. However, the mechanisms involved in this process are still unclear. In the present study, we determined the kinetics of RCMV-accelerated TVS in a rat heart transplant model. Acute RCMV infection enhances the development of TVS in rat heart allografts, and this process is initiated between 21 and 24 days posttransplantation. The virus is consistently detected in the heart grafts from day 7 until day 35 posttransplantation but is rarely found at the time of graft rejection (day 45 posttransplantation). Grafts from RCMV-infected recipients had upregulation of chemokine expression compared to uninfected controls, and the timing of this increased expression paralleled that of RCMV-accelerated neointimal formation. In addition, graft vessels from RCMV-infected grafts demonstrate the increased infiltration of T cells and macrophages during periods of highest chemokine expression. These results suggest that CMV-induced acceleration of TVS involves the increased graft vascular infiltration of inflammatory cells through enhanced chemokine expression.
引用
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页码:2182 / 2194
页数:13
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