RELEASE OF INTERLEUKIN-1-BETA ASSOCIATED WITH POTENT CYTOCIDAL ACTION OF STAPHYLOCOCCAL ALPHA-TOXIN ON HUMAN-MONOCYTES
RELEASE OF INTERLEUKIN-1-BETA ASSOCIATED WITH POTENT CYTOCIDAL ACTION OF STAPHYLOCOCCAL ALPHA-TOXIN ON HUMAN-MONOCYTES
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DOI：
10.1128/iai.57.11.3512-3519.1989
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发表时间：
1989-11-01
影响因子：
3.1
通讯作者：
HUGO, F
中科院分区：
文献类型：
--
作者：
BHAKDI, S;MUHLY, M;HUGO, F
金黄色葡萄球菌α毒素在人体中的致病相关性一直存在争议，因为人们认为人体细胞对这种溶细胞素的细胞毒性作用表现出天然抗性。继我们先前证明人类血小板代表毒素攻击的敏感靶标之后，我们现在已经鉴定出单核细胞作为第二种高度脆弱的人类细胞种类，其屈服于低剂量（20 ng/ml）的α毒素的攻击。α-毒素的细胞毒性作用反映在细胞ATP的快速消耗中，该消耗在30分钟内基本上完成。人血浆蛋白的存在提供了针对毒素作用的单核细胞的一些保护。在10%自体血清中，ATP耗竭开始于80至300 ng毒素/ml。亚细胞溶解剂量刺激肿瘤坏死因子α的释放，该过程在50%血清存在下略微加重。杀细胞毒素剂量必然引起大量白细胞介素-1 β的释放。来自培养的细胞，在应用毒素后60分钟，在细胞上清液中该单核因子的水平通常超过10 ng/ml。初步证据表明，这是由于细胞内白细胞介素-1的加工，而不是从头合成的细胞因子。在存在抗α毒素的中和单克隆抗体的情况下，所有注意到的作用均被消除。通过其引起单核细胞释放细胞因子和攻击血小板的能力，α-毒素可能引发与葡萄球菌感染发病机制相关的细胞事件。
The pathogenetic relevance of Staphylococcus aureus alpha-toxin in humans has been debated because human cells have been thought to display a natural resistance toward the cytotoxic action of this cytolysin. Following our previous demonstration that human platelets represent sensitive targets for toxin attack, we have now identified monocytes as a second, highly vulnerable human cell species that succumb to attack by low doses (20 ng/ml) of alpha-toxin. The cytotoxic action of alpha-toxin is reflected in a rapid depletion of cellular ATP that is essentially complete within 30 min. The presence of human plasma proteins affords some protection of monocytes against the action of the toxin. In 10% autologous serum, ATP depletion commences at 80 to 300 ng of toxin per ml. Subcytolytic doses stimulate the release of tumor necrosis factor alpha, a process that is slightly accentuated in the presence of 50% serum. Cytocidial toxin doses unfailingly cause the release of large amounts of interleukin-1.beta. from cultured cells, with levels of this monokine generally exceeding 10 ng/ml in the cell supernatants 60 min after application of toxin. Initial evidence suggests that this is due to processing of intracellular interleukin-1 rather than to de novo synthesis of the cytokine. All noted effects are abrogated in the presence of a neutralizing monoclonal antibody against alpha-toxin. Through its capacity to provoke cytokine release from monocytes and its attack on platelets, alpha-toxin may initiate cellular events that are relevant to the pathogenesis of staphylococcal infection.