Time-related effects of cytomegalovirus infection on the development of chronic renal allograft rejection in a rat model.
Cytomegalovirus (CMV) infection is a risk factor for chronic allograft rejection. The histological findings of chronic renal allograft rejection include inflammation, vascular intimal thickening, glomerulosclerosis, tubular atrophy and fibrosis. We have developed a rat model of renal transplantation in which transplants, after an early inflammatory episode, end up with chronic rejection within 60 days. During the early phase of the process in this model, CMV increased and prolonged the inflammatory response, the expression of adhesion molecules, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and their ligands, lymphocyte function antigen-1 and very late antigen-4 in the graft. Simultaneously, the production of various growth factors, such as transforming growth factor beta, platelet-derived growth factor and connective tissue growth factor was upregulated, which induce smooth muscle cell proliferation in the vascular wall and collagen synthesis by fibroblasts. Chronic rejection developed within 20 days in CMV-infected grafts. In summary, CMV infection accelerated and enhanced the early immune response, the induction of growth factors and collagen synthesis, and the development of chronic rejection in renal allografts.
Lautenschlager
I
I
Department of Virology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. Iremli.Lautenschlager@huch.fi
Soots
A
A
Krogerus
L
L
Inkinen
K
K
Kloover
J
J
Loginov
R
R
Holma
K
K
Kauppinen
H
H
Bruggeman
C
C
Ahonen
J
J
D000818:Animals; D003094:Collagen / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000821:virology; D004195:Disease Models, Animal; D006084:Graft Rejection; D006133:Growth Substances / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016030:Kidney Transplantation / Q000276:immunology; D008213:Lymphocyte Activation; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D006133:Growth Substances; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D003094:Collagen