Effects of staphylococcal enterotoxins on human neutrophil functions and apoptosis

Staphylococcal enterotoxins have marked effects on the properties of T cells and monocytes and have recently been reported to affect neutrophil function. In this study, we investigated the abilities of staphylococcal enterotoxins A and B and toxic shock syndrome toxin 1 to affect respiratory burst activity and to delay apoptosis in human neutrophils. When cultures containing approximately 97% neutrophils were tested, the toxins all delayed neutrophil apoptosis in a dose-dependent manner and induced the expression of FcgammaRI on the neutrophil cell surface. These effects on apoptosis and expression of FcgammaRI were largely abrogated by the addition of a neutralizing anti-gamma interferon antibody. Similarly, the effects of these toxins on phorbol ester-induced chemiluminescence were decreased after neutralization of gamma interferon. These effects on neutrophil function were mimicked by the addition of conditioned medium from peripheral blood mononuclear cells incubated with the toxins, and again, neutralizing anti-gamma interferon antibodies largely negated the effects. However, when highly purified neutrophils prepared by immunodepletion of T cells and major histocompatibility complex class II-expressing cells were analyzed, the toxins were without effect on apoptosis and FcgammaRI expression, but granulocyte-macrophage colony-stimulating factor and gamma interferon could still delay apoptosis. These data indicate that these toxins have no direct effect on neutrophil apoptosis but can act indirectly via the production of T-cell-derived and monocyte-derived cytokines. It is noteworthy that such effects are detected in neutrophil suspensions containing only 3% contamination with T cells and other mononuclear cells.