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.