We studied the influence of staphylococcal
toxic shock syndrome toxin 1 and streptococcal erythrogenic (pyrogenic) toxin A (ETA) on intact and
digitonin-permeabilized human polymorphonuclear granulocytes (PMNs). As was shown by reversed-phase high-performance liquid chromatography analysis,
toxic shock syndrome toxin 1 or ETA alone, in the absence of any additional stimulus, did not induce the generation of the
chemoattractant leukotriene B4 (
LTB4) from PMNs in a wide range of concentrations. In addition, pretreatment of intact PMNs with either toxin potentiated formyl-
methionyl-leucyl-phenylalanine (fMLP)- and washed Staphylococcus aureus cell-induced generation of
LTB4 in a time- and dose-dependent manner. This increase included
LTB4 as well as its inactive omega-oxidated compounds. Further studies revealed evidence that toxin exposure was accompanied by enhanced cellular receptor expression for fMLP as well as for
LTB4. The intrinsic
GTPase activity of membrane fractions was modulated by both toxins. Short-term incubation with ETA increased the
GTPase activity of PMNs up to 141%. Inhibitory effects were obtained when
GTP-binding protein functions were stimulated with
sodium fluoride (NaF). In addition, specific binding of
Gpp(NH)p to
GTP-binding protein was inhibited by both toxins during the first 10 min of incubation and was restored at later times of incubation. Our data therefore suggest that both toxins significantly affect the signal transduction pathways of human PMNs, which results in immunomodulatory functions.