Brain death in combination with warm ischemic stress during isolation procedures induces the expression of crucial inflammatory mediators in the isolated islets

Yukihiko Saito, Masafumi Goto, Kozue Maya, Norihiko Ogawa, Keisei Fujimori, Yoshimochi Kurokawa, Susumu Satomi

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)775-782
Number of pages8
JournalCell Transplantation
Volume19
Issue number6-7
DOIs
Publication statusPublished - 2010 Nov 1

Keywords

  • Brain death
  • Islets
  • Monocyte chemoattractant protein-1 (MCP-1)
  • Tissue factor (TF)
  • Transplantation

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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