GTP-BINDING PROTEINS ARE INVOLVED IN THE MODULATED ACTIVITY OF HUMAN NEUTROPHILS TREATED WITH THE PANTON-VALENTINE LEUKOCIDIN FROM STAPHYLOCOCCUS-AUREUS
GTP-BINDING PROTEINS ARE INVOLVED IN THE MODULATED ACTIVITY OF HUMAN NEUTROPHILS TREATED WITH THE PANTON-VALENTINE LEUKOCIDIN FROM STAPHYLOCOCCUS-AUREUS
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DOI：
10.1128/iai.62.12.5281-5289.1994
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发表时间：
1994-12-01
影响因子：
3.1
通讯作者：
KONIG, W
中科院分区：
文献类型：
--
作者：
HENSLER, T;KOLLER, M;KONIG, W
在与来自金黄色葡萄球菌V8菌株的Panton-Valentine杀白细胞素（Luk-PV）孵育后，人多形核白细胞（PMN）产生大量的白三烯B-4（LTB（4））。我们发现，GTP结合蛋白（G蛋白）参与了Luk-PV激活的PMN信号转导，霍乱和百日咳毒素对异源三聚体G蛋白的ADP核糖基化降低了Luk-PV诱导的LTB（4）产生。与此相反，ADP核糖基化的低分子量G蛋白rho和rac肉毒梭菌外切酶C3增加了Luk-PV诱导的LTB，合成。随后的刺激卢克-PV处理的中性粒细胞的钙离子载体A23187，氟化钠，或甲酰甲硫氨酰-亮氨酰-苯丙氨酸显着抑制。这种下降是由G蛋白功能的损失，包括GTP酶活性和GTP结合能力。用低量的Luk-PV获得了G蛋白功能的增加。除了调制G蛋白功能，ADP核糖基化的24-，40-和45-kDa的蛋白质的卢克-PV检测。如在对照实验中所示，ADP-核糖基化的24-kDa蛋白不是C.肉毒杆菌外切酶C3。将ras p21引入毛地黄皂苷透化的PMN对随后的Luk-PV刺激没有影响。此外，经Luk-PV处理的PMNs的ras p21、ras GAP和5-脂氧合酶易位到膜中，LTB（4）和甲酰甲硫氨酰亮氨酰苯丙氨酸的趋化性膜受体的表达也显著减少。
Significant amounts of leukotriene B-4 (LTB(4)) are generated by human polymorphonuclear neutrophils (PMNs) after incubation with the Panton-Valentine leukocidin (Luk-PV) from Staphylococcus aureus V8 strains. We showed that GTP-binding proteins (G proteins) are involved in the Luk-PV-activated signal transduction of PMNs, ADP-ribosylation of heterotrimeric G proteins by cholera and pertussis toxins decreased the Luk-PV-induced LTB(4)-generation. In contrast, ADP-ribosylation of the low-molecular-weight G proteins rho and rac by Clostridium botulinum exoenzyme C3 increased the Luk-PV-induced LTB, synthesis. The subsequent stimulation of Luk-PV-treated PMNs by either calcium ionophore A23187, sodium fluoride, or formylmethionyl-leucyl-phenylalanine was significantly inhibited. This decrease was paralleled by a loss of G-protein functions, including GTPase activity and GTP-binding capacity. An increase of G-protein functions was obtained with low amounts of Luk-PV. In addition to the modulated G-protein functions, ADP-ribosylation of 24-, 40-, and 45-kDa proteins by Luk-PV was detected. As shown in control experiments, the ADP-ribosylated 24-kDa proteins were not substrates for C. botulinum exoenzyme C3. Introduction of ras p21 into digitonin-permeabilized PMNs was without effect on subsequent Luk-PV stimulation. In addition, the translocation of ras p21, ras GAP, and 5-lipoxygenase into the membrane of Luk-PV-treated PMNs, as well as the expression of chemotactic membrane receptors for LTB(4) and formylmethionyl leucyl phenylalanine,,vas significantly diminished.