INDUCTION OF HEAT-SHOCK PROTEINS BY BACTERIAL TOXINS, LIPID MEDIATORSAND CYTOKINES IN HUMAN-LEUKOCYTES

We studied the influence of a lipid mediator (12-hydroxyeicosatetraeno ic acid, 12-HETE), cytokines (IL-6 and TNF-alpha) and different bacter ial toxins (alveolysin; exfoliative toxin; toxic shock syndrome toxin 1, TSST-1 and erythrogenic toxin A, ETA) on the expression of heat sho ck proteins (hsps) in isolated human leucocytes. 12-HETE induces the e xpression of individual heat shock proteins (65- and 83 kDa) protein i n human leukocytes (lymphocytes, monocytes, basophilic granulocytes; L MBs). As was shown by Western blotting (anti-hsp72), IL-6 or TNF-alpha induced hsps preferentially in human LMBs and PMNs, respectively. Amo ng the toxins, ETA and TSST-1 were potent inducers of hsps at low toxi n concentrations (10 ng/ml). Alveolysin led to the expression of hsps at hemolytic concentrations (1 HU; 700 ng/ml) whereas at subhemolytic concentrations (7 ng/ml), no heat shock response was observed. The ind uction of heat shock proteins was also accompanied by increased mRNA l evels for hsp70 as determined by PCR analysis. In contrast, exfoliativ e toxin led to a reduction of the hsp signal in PMNs as determined by Western blotting. Finally, it was demonstrated that PMNs which had bee n pretreated with TNF-alpha and therefore expressed intracellular hsps were more resistant to cytolytic attack by leukocidin than untreated cells.