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APOPTOSIS IN KIDNEY AND PANCREAS ALLOGRAFT BIOPSIES

2004; Wolters Kluwer; Volume: 78; Linguagem: Inglês

10.1097/00007890-200407271-00395

1534-6080

Sabrina Gomes de Oliveira, Dino Martini, Tércio Genzini, Marcelo Perosa, Wagner V. Dominguez, Dimitri Bordon Espinhel Marinotto, Tabata Tavares, João Egídio Romão, Hugo Abensur, Irene L. Noronha,

Pancreatic and Hepatic Oncology Research

O382* Aims: Kidney-pancreas transplantation is an established procedure for the treatment of diabetic patients with chronic renal insufficiency. In this type of transplantation, allograft rejection represents an important complication. The cellular immune response involved in allograft rejection has been extensively studied. However, the participation of apoptosis in this process, particularly in pancreas allograft rejection has not been elucidated. The aim of this study was to analyze the occurrence of apoptotic cells in kidney and pancreas allograft biopsies by TUNEL method to evaluate the participation of apoptosis in the mechanism of allograft rejection. Methods: Kidney and pancreas biopsies (n=56) from patients submitted to simultaneous pancreas-kidney transplantation were classified into three groups according to clinical and histological criteria: acute rejection (AR), chronic rejection (CR), and transplant cases without evidence of rejection (No rejection). Normal renal tissue obtained from kidney donors was used as control group (Normal kidney) and normal pancreas tissue obtained from pancreas used for islet isolation was also used as control group (Normal pancreas). Formalin-fixed paraffin biopsies were used to identify apoptosis (cells with DNA fragmentation) by the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin end labeling (TUNEL) method. Quantification of apoptotic cells was carried out by counting positively TUNEL stained cells (presented as cells/mm2). Results: Table 1. Average number of apoptotic cells (mean±SEM; *p<0.05 vs Normal pancreas and vs Kidney acute rejection).FigureIn normal kidney, only few apoptotic cells were observed. In contrast, in AR the TUNEL signal was detected in the nuclei of numerous mononuclear cells infiltrating the interstitium. In addition, apoptotic cells were detected in tubular epithelial cells and occasionally in endothelial cells. In AR of pancreas biopsies TUNEL staining was observed in acinar cells, in interstitial cells and rarely in pancreatic islets. The number of apoptotic cells observed in AR in pancreas biopsies was significantly higher compared to kidney AR. Conclusions: These results demonstrate that apoptosis occurs in kidney and pancreas allograft biopsies, markedly in acute rejection in pancreas biopsies. Although apoptosis may reflect a mechanism of down regulation of the allograft immune response by eliminating infiltrating cells, the elimination of graft cells may result in graft damage, particularly in pancreas transplantation.