Rat cytomegalovirus infection in kidney allograft recipients is associated with increased expression of intracellular adhesion molecule-1 vascular adhesion molecule-1, and their ligands leukocyte function antigen-1 and very late antigen-4 in the graft.
BACKGROUND
Cytomegalovirus (CMV) infection is suggested to be a risk factor for chronic rejection. We have recently shown that rat CMV (RCMV) increases the inflammatory response and accelerates chronic rejection in a model of rat kidney allograft. In this study, the early inflammatory response and time-related expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and their ligands, leukocyte function antigen-1 (LFA-1) and very late antigen-4 (VLA-4), in the grafts were investigated in RCMV-infected rats and compared to noninfected rats developing chronic rejection.


METHODS
Transplantations were performed in a rat strain combination of DA (RT1a)->BN (RT1n) receiving triple drug immunosuppression. One group of rats was infected with RCMV, and the other was left uninfected. The grafts were harvested at different time points after transplantation. The adhesion molecules, their ligands and activation markers, MHC class II antigens and interleukin-2-receptors (IL-2-R), were demonstrated by monoclonal antibodies and immunoperoxidase staining from frozen sections of the grafts. Graft histology was evaluated according to the Banff criteria.


RESULTS
RCMV caused a significant, prolonged increase of VCAM-1 and ICAM-1 expression in the vascular endothelium compared to the noninfected grafts. Also, the number of cells expressing activation markers, LFA-1 and VLA-4 was significantly enhanced in these animals. Significantly enhanced histological changes of chronic rejection were seen in the RCMV-infected group.


CONCLUSIONS
Prolonged, increased expression of ICAM-1 and VCAM-1, and increased numbers of inflammatory cells expressing their ligands in the CMV infected grafts, were associated with accelerated chronic allograft nephropathy.
Department of Medical Microbiology, University of Maastricht, The Netherlands.
J S
JS
Kloover
A P
AP
Soots
L A
LA
Krogerus
H O
HO
Kauppinen
R J
RJ
Loginov
K L
KL
Holma
C A
CA
Bruggeman
P J
PJ
Ahonen
I T
IT
Lautenschlager
D000818:Animals; D003586:Cytomegalovirus Infections / Q000378:metabolism*; D006084:Graft Rejection; D039041:Integrin alpha4beta1; D016023:Integrins / Q000096:biosynthesis*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis*; D051381:Rats; D011914:Rats, Inbred BN; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis*; D014184:Transplantation, Homologous; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*
D039041:Integrin alpha4beta1; D016023:Integrins; D016169:Lymphocyte Function-Associated Antigen-1; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1