Moulding D A, Walter C, Hart C A, Edwards S W
School of Biological Sciences, University of Liverpool, Liverpool L69 7ZB, United Kingdom.
Infect Immun. 1999 May;67(5):2312-8. doi: 10.1128/IAI.67.5.2312-2318.1999.
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.
葡萄球菌肠毒素对T细胞和单核细胞的特性有显著影响，最近有报道称其会影响中性粒细胞功能。在本研究中，我们调查了葡萄球菌肠毒素A、B以及中毒性休克综合征毒素1影响人中性粒细胞呼吸爆发活性和延迟细胞凋亡的能力。当检测含有约97%中性粒细胞的培养物时，这些毒素均以剂量依赖的方式延迟中性粒细胞凋亡，并诱导FcγRI在中性粒细胞表面表达。加入中和性抗γ干扰素抗体后，这些对细胞凋亡和FcγRI表达的影响在很大程度上被消除。同样，中和γ干扰素后，这些毒素对佛波酯诱导的化学发光的影响也减弱。用与毒素孵育的外周血单核细胞的条件培养基处理可模拟这些毒素对中性粒细胞功能的影响，并且中和性抗γ干扰素抗体同样在很大程度上消除了这些影响。然而，当分析通过免疫去除T细胞和表达主要组织相容性复合体II类分子的细胞制备的高度纯化的中性粒细胞时，这些毒素对细胞凋亡和FcγRI表达没有影响，但粒细胞-巨噬细胞集落刺激因子和γ干扰素仍可延迟细胞凋亡。这些数据表明，这些毒素对中性粒细胞凋亡没有直接影响，但可通过T细胞来源和单核细胞来源的细胞因子间接发挥作用。值得注意的是，在仅含有3% T细胞和其他单核细胞污染的中性粒细胞悬液中也检测到了这种效应。
