Heat shock attenuates oxidation and accelerates apoptosis in human neutrophils

Background. The heat shock, response entails the increased expression of he at shock proteins (hsp) which are capable of protecting cells from subseque nt metabolic insults. Here we are interested in determining whether activat ion of the heat shock response might affect polymorphonuclear leukocyte (PM N) function and/or longevity. Methods. Freshly isolated human PMN were either left at 37 degrees C or sub jected to a 43 degrees C heat shock treatment (60 min) and subsequently ret urned to 37 degrees C. During the course of the recovery period a number of parameters were examined for the control and heat shock-treated neutrophil s: the relative expression of the highly stress-inducible hsp72; respirator y burst activity as measured by intracellular peroxidation in response to p horbol ester addition; cell-surface expression of CD16; and finally, the ex tent of apoptosis as determined by both annexin V staining and nuclear prop idium iodide staining. Results. Heat shock treatment resulted in a progressive increase in hsp72 p roduction, peaking at 8 h following return of the cells to 37 degrees C. Ne t intracellular oxidant production was diminished by 46% immediately follow ing the heat shock treatment and deteriorated even further over the next 4 h. Finally, a significant early increase in the rate of apoptosis was obser ved in the cells subjected to the hyperthermic treatment. This increase in the heat-induced rate of apoptosis was associated with a marked reduction i n cell-surface CD16 levels. Conclusions. By decreasing PMN oxidative functions and by accelerating thei r apoptotic demise, it would appear that heat shock is anti-inflammatory an d not cytoprotective for PMN. (C) 1999 Academic Press.