Induction of heat shock protein 72 prevents neutrophil-mediated human endothelial cell necrosis
J. H. Wang, H. P. Redmond, R. W. Watson, C. Condron and D. Bouchier-Hayes
Royal College of Surgeons in Ireland, Department of Surgery, Beaumont Hospital, Dublin, Ireland.
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). DESIGN: 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.
CONCLUSION: 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.
