An Experimental Model of Chronic Renal Allograft Rejection in the Rat Using Triple Drug Immunosuppression1

Soots, Anu; Lautenschlager, Irmeli; Krogerus, Leena; Saarinen, O.; Ahonen, J

doi:10.1097/00007890-199801150-00009

Cited by 38 publications

(27 citation statements)

References 12 publications

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“…We have recently developed an experimental model in which, after an early inflammatory episode, rat renal allografts develop chronic rejection under triple-drug immunosuppressive therapy within 60 days after transplantation [26]. We studied the early phase of the process in detail and recorded that the peak of inflammation occurs 5-10 days after transplantation.…”

Section: Introductionmentioning

confidence: 99%

Time-Related Effects of Cytomegalovirus Infection on the Development of Chronic Renal Allograft Rejection in a Rat Model

Lautenschlager

Soots²,

Krogerus³

et al. 1999

Intervirology

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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.

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Section: Introductionmentioning

confidence: 99%

Time-Related Effects of Cytomegalovirus Infection on the Development of Chronic Renal Allograft Rejection in a Rat Model

Lautenschlager

Soots²,

Krogerus³

et al. 1999

Intervirology

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“…The rat is a popular model for transplantation research, and various strain combinations exist to study chronic renal allograft nephropathy/vasculopathy (2)(3)(4)(5). Noninvasive imaging of renal grafts in these models could provide valuable information regarding the onset and progression of abnormalities, such as those associated with rejection or response to treatment.…”

mentioning

confidence: 99%

MRI and ultrasonographic detection of morphologic and hemodynamic changes in chronic renal allograft rejection in the rat

Gaschen

Schuurman

Bruttel

et al. 2001

J. Magn. Reson. Imaging

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“…In our model, after a mild early inflammatory episode, characteristical histological findings of chronic rejection were developed within 60 days after transplantation [20]. In the follow-up, the induction of adhesion molecules occurred between days 5 and 15 and the expression peaked on day 5 after transplantation in all of the renal structures investigated.…”

Section: Discussionmentioning

confidence: 67%

“…We have previously developed a model of chronic rejection in which the transplantations are performed in a high-responder rat strain combination which, under immuno-suppression of triple drug treatment with steroids, azathioprine and cyclosporine after an early inflammatory episode, develops chronic rejection within 40-60 days [20]. In this study, we investigate the sequential expression of ICAM-1 and VCAM-1 on various vascular structures and the presence of their ligand molecules, LFA-1 and VLA-4 expressing leukocytes in rat renal allografts during the development of chronic rejection.…”

Section: Introductionmentioning

confidence: 99%

Sequential analysis of adhesion molecules and their ligands in rat renal allografts during the development of chronic rejection

et al. 2000

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Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are important in endothelial cellleukocyte interactions. In this sequential study, the expression of ICAM-1 and VCAM-1 and their ligands LFA-1 and VLA-4 as well as major histocompatibility complex class I1 antigens (MHC class II), and interleukin-2-receptor (IL-2R) were investigated during the development of chronic renal allograft rejection in a rat model. The time-related expression of adhesion molecules and their ligands in the graft was correlated to the chronic allograft damage index (CADI). In association with an initial short immune activation, there was a significant ICAM-1 and VCAM-1 induction in the vascular endothelium and the tubular epithelium. In the interstitium, there was infiltration of lymphocytes expressing ligand molecules VLA-4 and LFA-l, as well as activation markers MHC class I1and IL-2R. Thereafter, the expression declined together with the increase of CADI-values. In end-stage chronic rejection, there was practically no expression of ICAM-1 and VCAM-1. In the interstitium, there were only few ligand-expressing leukocytes. In conclusion, adhesion molecules and their ligands are involved in the induction phase of the process but no longer in the later stages of chronic rejection.

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An Experimental Model of Chronic Renal Allograft Rejection in the Rat Using Triple Drug Immunosuppression1

Abstract: In conclusion, in the DA-->BN combination with triple drug treatment, early mild inflammation was followed by the development of chronic rejection and can be used as an experimental model that resembles the clinical situation in renal transplantation.

Cited by 38 publications

References 12 publications

Time-Related Effects of Cytomegalovirus Infection on the Development of Chronic Renal Allograft Rejection in a Rat Model

Time-Related Effects of Cytomegalovirus Infection on the Development of Chronic Renal Allograft Rejection in a Rat Model

MRI and ultrasonographic detection of morphologic and hemodynamic changes in chronic renal allograft rejection in the rat

Sequential analysis of adhesion molecules and their ligands in rat renal allografts during the development of chronic rejection

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