Rat cytomegalovirus infection and chronic kidney allograft rejection.
To investigate the effect of cytomegalovirus (CMV) infection on the development of experimental chronic kidney allograft rejection, orthotopic kidney allografts from DA donors (Ag-B4, RT1a1) to WF (Ag-B2, RT1u) recipients were used. The rats received cyclosporine A (CsA) for 12 weeks. A group of recipients was infected with 10(5) plaque-forming units of rat CMV (RCMV), and another group was left non-infected and used as controls. The grafts were removed 12 weeks after transplantation. RCMV infection significantly enhanced the development of chronic kidney allograft rejection as follows: the intensity of interstitial inflammation (P < 0.025), particularly the degree of pyroninophilic cells in the inflammatory infiltrate (P < 0.025); the glomeruli mesangial matrix increase (P < 0.05) and capillary basement membrane thickening (P < 0.01); the extent of endothelial cell swelling (P < 0.025) and intimal proliferation (P < 0.025) in the graft vasculature; and the extent of tubular epithelial atrophy (P < 0.025). The chronic allograft damage index (CADI) was significantly increased to 4.2 +/- 0.9 in RCMV-infected allografts, compared with 0.8 +/- 0.4 in non-infected (P < 0.02). At the molecular level, RCMV infection significantly increased vascular endothelial (P < 0.05) and tubular epithelial (P < 0.01) ICAM-1 expression. Viral antigens were detected in tubular epithelial cells and in some inflammatory cells.
Koskinen
P K
PK
Transplantation Laboratory, University of Helsinki, Finland.
Yilmaz
S
S
Kallio
E
E
Bruggeman
C A
CA
Häyry
P J
PJ
Lemström
K
K
D000818:Animals; D002908:Chronic Disease; D003586:Cytomegalovirus Infections / Q000150:complications*; D006084:Graft Rejection; D016030:Kidney Transplantation / Q000009:adverse effects*; D051381:Rats; D011920:Rats, Inbred WF; D014184:Transplantation, Homologous