Induction of heat shock protein 72 prevents neutrophil-mediated human endothelial cell necrosis.
OBJECTIVE
To examine the hypothesis that induction of heat shock proteins in human endothelial cells (ECs) by either heat shock or sodium arsenite could prevent subsequent EC necrosis induced by activated human polymorphonuclear neutrophil leukocytes (PMNs).


METHODS
Cultures of ECs were exposed to heat shock (42 degrees C, 30 to 60 minutes) or sodium arsenite (40 to 320 mumol/L) for 6 hours to induce the expression of a heat shock protein of 72-kd molecular weight (HSP-72). Activated PMNs were subsequently added to these ECs for 24 hours to evaluate the ability of HSP-72 to prevent activated PMN-mediated EC necrosis.


RESULTS
Neither EC necrosis nor apoptosis was induced by heat shock. Sodium arsenite (40 to 80 mumol/L) did not induce EC necrosis, although 320-mumol/L sodium arsenite caused a significant increase in EC necrosis. Sodium arsenite (80 to 320 mumol/L) also induced dose-dependent EC apoptosis. Endothelial cells exposed to heat shock and sodium arsenite (40 and 80 mumol/L) significantly attenuated subsequent EC necrosis induced by activated PMNs. However, sodium arsenite at 320 mumol/L aggravated activated PMN-mediated EC necrosis. Expression of HSP-72 was detected after ECs were treated both with heat shock and sodium arsenite (40 to 320 mumol/L) for 6 hours.


CONCLUSIONS
Induction of HSP-72 in ECs by a thermal or nonthermal mechanism could prevent activated PMN-mediated EC necrosis, which may favor increased vascular permeability during systemic inflammatory response syndrome.
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D018053:Arsenites / Q000494:pharmacology; D004727:Endothelium / Q000187:drug effects / Q000473:pathology*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D009336:Necrosis / Q000276:immunology / Q000503:physiopathology*; D009504:Neutrophils / Q000502:physiology*; D016897:Respiratory Burst / Q000502:physiology; D017670:Sodium Compounds / Q000494:pharmacology
D018053:Arsenites; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D017670:Sodium Compounds; C017947:sodium arsenite