PMID- 20573302 OWN - NLM STAT- MEDLINE DCOM- 20110131 LR - 20101019 IS - 1555-3892 (Electronic) IS - 0963-6897 (Linking) VI - 19 IP - 6 DP - 2010 TI - Brain death in combination with warm ischemic stress during isolation procedures induces the expression of crucial inflammatory mediators in the isolated islets. PG - 775-82 LID - 10.3727/096368910X508889 [doi] AB - Tissue factor (TF) and monocyte chemoattractant protein-1 (MCP-1) expressed on the islets have been identified as the main trigger of the instant blood-mediated inflammatory reaction (IBMIR) in islet transplantation. Because the key steps that directly induce TF and MCP-1 remain to be determined, we focused on the influence of brain death (BD) on TF and MCP-1 expression in the pancreatic tissues and isolated islets using a rodent model. TF and MCP-1 mRNA levels in the pancreatic tissues were similar between the BD and the control group. However, TF and MCP-1 mRNA in the fresh islets of the BD group were significantly higher than that of the control group (p < 0.01). BD may thus be suggested to be of great importance as an initiator of TF and MCP-1 induction in the isolated islets. Furthermore, the upregulation of crucial inflammatory mediators induced by BD could be exacerbated by warm ischemic damage during digestion procedures. In the present study, the islet yield and purity were affected by BD. However, almost no influences were observed with respect to islet viability, indicating that the expression of inflammatory mediators rather than islet viability is more susceptible to BD. According to the change in time course of TF and MCP-1 expression in the isolated islets, the selected time point for islet infusion in current clinical islet transplantation was thus shown to be at its worst level, at least with respect to the damage caused by BD and ischemic stress. In conclusion, BD in combination with warm ischemic stress during isolation procedures induces a high expression of TF and MCP-1 in the isolated islets. In order to reduce the expression of crucial inflammatory mediators in the islet grafts, the management of the pancreas from brain-dead donors with early anti-inflammatory treatments is thus warranted. FAU - Saito, Yukihiko AU - Saito Y AD - Division of Advanced Surgical Science and Technology, Tohoku University, Sendai, Japan. FAU - Goto, Masafumi AU - Goto M FAU - Maya, Kozue AU - Maya K FAU - Ogawa, Norihiko AU - Ogawa N FAU - Fujimori, Keisei AU - Fujimori K FAU - Kurokawa, Yoshimochi AU - Kurokawa Y FAU - Satomi, Susumu AU - Satomi S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100623 PL - United States TA - Cell Transplant JT - Cell transplantation JID - 9208854 RN - 0 (Chemokine CCL2) RN - 0 (Inflammation Mediators) RN - 0 (RNA, Messenger) RN - 9035-58-9 (Thromboplastin) SB - IM MH - Animals MH - Brain Death/*pathology MH - Chemokine CCL2/genetics/metabolism MH - Gene Expression Regulation MH - Inflammation Mediators/*metabolism MH - Islets of Langerhans/*metabolism MH - Male MH - Organ Preservation/*methods MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Rats, Inbred Lew MH - Thromboplastin/genetics/metabolism MH - Time Factors MH - Tissue Survival MH - *Warm Ischemia EDAT- 2010/06/25 06:00 MHDA- 2011/02/01 06:00 CRDT- 2010/06/25 06:00 PHST- 2010/06/25 06:00 [entrez] PHST- 2010/06/25 06:00 [pubmed] PHST- 2011/02/01 06:00 [medline] AID - ct2266saito [pii] AID - 10.3727/096368910X508889 [doi] PST - ppublish SO - Cell Transplant. 2010;19(6):775-82. doi: 10.3727/096368910X508889. Epub 2010 Jun 23.