Heat shock attenuates oxidation and accelerates apoptosis in human neutrophils

Background. The heat shock, response entails the increased expression of heat shock proteins (hsp) which are capable of protecting cells from subsequent metabolic insults. Here we are interested in determining whether activation of the heat shock response might affect polymorphonuclear leukocyte (PMN) function and/or longevity. Methods. Freshly isolated human PMN were either left at 37 degrees C or subjected to a 43 degrees C heat shock treatment (60 min) and subsequently returned to 37 degrees C. During the course of the recovery period a number of parameters were examined for the control and heat shock-treated neutrophils: the relative expression of the highly stress-inducible hsp72; respiratory burst activity as measured by intracellular peroxidation in response to phorbol ester addition; cell-surface expression of CD16; and finally, the extent of apoptosis as determined by both annexin V staining and nuclear propidium iodide staining. Results. Heat shock treatment resulted in a progressive increase in hsp72 production, peaking at 8 h following return of the cells to 37 degrees C. Net intracellular oxidant production was diminished by 46% immediately following the heat shock treatment and deteriorated even further over the next 4 h. Finally, a significant early increase in the rate of apoptosis was observed in the cells subjected to the hyperthermic treatment. This increase in the heat-induced rate of apoptosis was associated with a marked reduction in cell-surface CD16 levels. Conclusions. By decreasing PMN oxidative functions and by accelerating their apoptotic demise, it would appear that heat shock is anti-inflammatory and not cytoprotective for PMN. (C) 1999 Academic Press.