Phenol-Soluble Modulin α3 Enhances the Human Neutrophil Lysis Mediated by Panton-Valentine Leukocidin

Phenol-Soluble Modulin α3 Enhances the Human Neutrophil Lysis Mediated by Panton-Valentine Leukocidin
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DOI:
10.1086/605332
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发表时间:
2009-09-01
影响因子:
6.4
通讯作者:
Hiramatsu, Keiichi
Hiramatsu, Keiichi
中科院分区:
医学2区
文献类型:
--
作者:
Hongo, Isamu;Baba, Tadashi;Hiramatsu, Keiichi

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潘通-瓦伦丁白细胞杀死素(PVL)一直被认为是严重金黄色葡萄球菌感染的关键毒素。PVL可能通过裂解人类多形核细胞(pmn)来破坏人体的防御系统。然而,最近,生物活性肽-酚溶性调节素(psm)-被认为是pmn裂解的主要参与者,而不是PVL。本研究旨在利用重组PVL毒素和中和PVL的单克隆抗体来解决关于人PMNs裂解原因的不确定性。重组PVL毒素对人中性粒细胞有较强的溶解活性,对小鼠中性粒细胞无明显的溶解活性。此外,菌株USA400 MW2和USA300 FPR3757培养上清液的裂解活性被抗pvl单克隆抗体完全中和。相反,在培养上清中含有的浓度下,酚溶性调节蛋白α 3(最有效的PSM肽)无法裂解人pmn。然而,酚溶性调节素- 3确实增强了pvl介导的人PMNs的裂解。
Panton-Valentine leukocidin (PVL) has long been considered a critical toxin in severe Staphylococcus aureus infection. PVL presumably breaches the body's defense system by lysing human polymorphonuclear cells (PMNs). Recently, however, bioactive peptides- phenol-soluble modulins (PSMs)-have been proposed as the main player in the lysis of PMNs, rather than PVL. This study aimed to resolve uncertainty concerning the cause of the lysis of human PMNs by using recombinant PVL toxins and PVL-neutralizing monoclonal antibodies. The recombinant PVL toxins showed strong lytic activity against human but not murine neutrophils. Moreover, the lytic activity of culture supernatants of strains USA400 MW2 and USA300 FPR3757 were completely neutralized by anti-PVL monoclonal antibodies. In contrast, phenol-soluble modulin alpha 3-the most potent PSM peptide-failed to lyse human PMNs at the concentrations contained in the culture supernatants. Phenol-soluble modulin alpha 3 did, however, enhance PVL-mediated lysis of human PMNs.