PMID- 12727475 OWN - NLM STAT- MEDLINE DCOM- 20040123 LR - 20061115 IS - 0966-3274 (Print) IS - 0966-3274 (Linking) VI - 11 IP - 1 DP - 2003 Jan-Mar TI - Oncogene expression on the syngeneic beta-cells of long-term surviving pancreatic grafts and better effects of interleukin-1 receptor (IL-1R) and IL-2Rbeta on the grafted beta-cells in LEW/Sea strain rats. PG - 49-56 AB - Thirty-two normal LEW/Sea rats were transplanted a piece of syngeneic pancreas between the peritoneum and abdominal muscle. Among them, 17 (68%) of the 25 rats that received pancreatic transplantation at 41-50 days of age had a surviving beta-cell mass at 5.5-7.1 months after transplantation. Among the 25 rats, 12 rats injected with interleukin-1 receptor (IL-1R) and IL-2Rbeta peptides at post-transplantation showed better surviving grafts at 5.5 months' observation. Only 2 (25%) of the other 7 young rats that received a pancreatic graft at 20 days of age had a small mass at 21 days post-transplantation. Flow cytometer (FCM) analyses showed that thymus OX40(+) (CD134(+)) T-cells were increased up to 37+/-4% at the graft rejection in the 13 old rats without the IL-R peptide injections. The 7 young rats had 99% of thymus OX40(+) T-cells. However, the 12 old rats injected with the IL-R peptides showed suppressed numbers of thymus OX40(+) T-cells (8-13+/-3%). The long-term surviving, but apoptotic, grafted beta-cells were stained positively both with anti-insulin monoclonal antibody (mAb) and with anti-c-erbB-2/human epidermal growth factor receptor (HER)-2/neu mAb. Expression of a c-erb family oncogene was shown on the pancreatic graft surviving for 7.1 months. Electron microscopic analysis of the grafted beta-cells showed abnormally large beta granules and loss of functioning mitochondria in the cytoplasm. In 18 (56%) of the 32 rats, the 220-bp and 380-bp specific products of insulin-degrading enzyme (IDE) gene were amplified using the polymerase chain reaction (PCR) of the liver DNA. Among the 18 rats, 6 rats expressed 2 extra hands of 280-bp and 700-bp in a correlation with the high levels of the transforming growth factor-alpha (TGF-alpha) cDNA of 120-bp which was amplified in the quantitative reverse-transcriptase (RT)-PCR of the liver cDNA. Among the selected 11 rats, 5 rats showed large amounts of the 120-bp TGF-alpha cDNA. Host pancreatic RT-PCR showed 235-bp or 250-bp bcl-2 and 181-bp bcl-xS gene products. The bcl-2 cDNA of the host pancreas was amplified actively when the pancreatic graft was being rejected. Exceptionally, the one female injected with the IL-R peptides showed a low level of the liver TGF-alpha cDNA together with the pancreatic expressions of Bax (140-bp), bcl-2 and like interleukin converting enzyme (LICE) (318-bp) cDNA. Insulin secretion from the grafted beta-cells and IL-1beta-induced Fas-mediated apoptosis of the beta-cells were suspected to be present at the same time in the female with the best graft survival. FAU - Nakatsuji, Tadako AU - Nakatsuji T AD - Department of Transfusion, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. nh80415@hama-med.ac.jp LA - eng PT - Journal Article PL - Netherlands TA - Transpl Immunol JT - Transplant immunology JID - 9309923 RN - 0 (IL2RB protein, human) RN - 0 (Il2rb protein, rat) RN - 0 (Interleukin-2 Receptor beta Subunit) RN - 0 (Receptors, Interleukin) RN - 0 (Receptors, Interleukin-1) RN - 9007-49-2 (DNA) SB - IM MH - Animals MH - DNA/metabolism MH - Female MH - Immunohistochemistry MH - Interleukin-2 Receptor beta Subunit MH - Islets of Langerhans/*immunology/metabolism MH - Male MH - Microscopy, Electron MH - Oncogenes/immunology/*physiology MH - Pancreas/pathology/ultrastructure MH - Pancreas Transplantation/*immunology MH - Rats MH - Rats, Inbred Lew MH - Receptors, Interleukin/*metabolism MH - Receptors, Interleukin-1/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2003/05/03 05:00 MHDA- 2004/01/24 05:00 CRDT- 2003/05/03 05:00 PHST- 2003/05/03 05:00 [pubmed] PHST- 2004/01/24 05:00 [medline] PHST- 2003/05/03 05:00 [entrez] AID - S0966-3274(02)00085-0 [pii] AID - 10.1016/S0966-3274(02)00085-0 [doi] PST - ppublish SO - Transpl Immunol. 2003 Jan-Mar;11(1):49-56. doi: 10.1016/S0966-3274(02)00085-0.