Pretransplant Induction of HSP-70 in Isolated Adult Pig Islets Decreases Early Islet Xenograft Survival

Abstract

The heat-induced HSP-70 expression protects rat islet single cells against lysis mediated by nitric oxide (NO), reactive oxygen, and streptozotocin. The present study was performed to investigate the potential antiinflammatory effect of pretransplant heat shock in adult pig islets for subsequent early islet xenograft survival. Maximum HSP-70 expression in freshly isolated pig islets was induced by hyperthermia at 43 degrees C for 90 min prior to islet regeneration at 37 degrees C for 4-6 h. Heat-stressed and sham-treated islets were incubated in 0.6 mM H2O2 or 1.5 mM Na-nitroprusside at 37 degrees C for 20 h. Early graft survival was evaluated in normoglycemic Lewis rats after simultaneous, contralateral transplantation of heat-shocked islets and sham-treated islets into the renal subcapsular space of the same recipient. Prior hyperthermia significantly reduced specific lysis of islets exposed to NO or H2O2, although protection was only marginal. No differences were observed between viability of heat-shocked and sham-treated islets after NO exposure. In contrast, prior heat shock increased islet viability after H2O2 treatment. The finding that hyperthermia reduced recovery of initially grafted pig insulin 48 h after transplantation by 30% compared to controls contrasted significantly with an increased insulin recovery in heat-exposed islets at the end of simultaneous 37 degrees C culture. The observation, that the heat-induced HSP-70 expression decreases early islet xenograft survival as reflected by recovery of grafted insulin, implies an enhancement of islet immunogenicity and the induction of apoptosis. Future experiments aiming at augmentation of intrinsic defense mechanisms should consider detrimental effects associated with induction of heat shock proteins.

Hyperbaric oxygenation of UW solution positively impacts on the energy state of porcine pancreatic tissue*

“…The synthesis of stress or heat shock proteins (HSPs) which enables the cell to survive in an otherwise lethal situation is crucial in islet isolation and purification processes [34]. The formation of heat shock proteins (e.g.…”

Human Islet Isolation and Distribution Efforts for Clinical and Basic Research

“…Exposure of islets to temperatures beyond their physiological range for an extended period of time negatively impacts their quality. It has been shown that hypothermic conditions (1-4 °C) drastically reduce the viability of mammalian cells [54], while high temperatures (43 °C) decrease the survival rates of early xenografts of pig islets in mice [55]. The Integrated Islet Distribution Program (IIDP) provides ColdMark ® and WarmMark ® indicators to detect undesirable temperature changes.…”

Transplantation of Long-term Cultured Porcine Islets in the Rat: Prolonged Graft Survival and Recipient Growth on Reduced Immunosuppression

“…The other recipient was sacrificed much later while (3,18), and is most likely caused by mediators produced by macrophages and can be prevented by NO inhibitors normoglycemic and showed plentiful AF-positive islets without infiltrate. Together these data suggest a tempo- (3,16). These data strongly point out the macrophage as the primary cell responsible for graft destruction, and rary functional deficit probably caused by loss of damaged graft tissue or due to the rapid weight gain of the support earlier observations that CsA can act directly on macrophages (8,15).…”