Gauduchon Valérie, Cozon Gregoire, Vandenesch François, Genestier Anne-Laure, Eyssade Nathalie, Peyrol Simone, Etienne Jerome, Lina Gerard
Centre National de Référence des Staphylocoques, INSERM E0230, IFR62 Laennec, Lyon, France.
J Infect Dis. 2004 Jan 15;189(2):346-53. doi: 10.1086/380909. Epub 2004 Jan 9.
Panton Valentine leukocidin (PVL) may be responsible for pulmonary necrosis in necrotizing Staphylococcus aureus pneumonia, a highly lethal infection. Commercial intravenous immunoglobulin (IVIg) preparations containing antibodies against PVL might have therapeutic value in this setting, as an adjunct to antimicrobial chemotherapy. To test this possibility, we determined anti-PVL antibody titers in commercial IVIg and the capacity of IVIg to prevent the cytopathic effects of PVL in vitro. Specific enzyme-linked immunosorbent assays based on purified recombinant PVL (rPVL) showed that IVIg contained specific anti-PVL antibodies. The cytotoxicity of rPVL and of crude culture supernatants of PVL-producing S. aureus strains were investigated by measuring ethidium-bromide incorporation by polymorphonuclear neutrophils (PMNs) in flow cytometric assays, as well as PMN ultrastructural changes by transmission electron microscopy. IVIg was found to neutralize pore formation and the cytopathic effect of both rPVL and S. aureus culture supernatants.
杀白细胞素(PVL)可能是导致坏死性金黄色葡萄球菌肺炎肺坏死的原因,这是一种极具致死性的感染。含有抗PVL抗体的商业静脉注射免疫球蛋白(IVIg)制剂在这种情况下可能具有治疗价值,可作为抗菌化疗的辅助手段。为了验证这种可能性,我们测定了商业IVIg中的抗PVL抗体滴度以及IVIg在体外预防PVL细胞病变效应的能力。基于纯化重组PVL(rPVL)的特异性酶联免疫吸附试验表明,IVIg含有特异性抗PVL抗体。通过流式细胞术检测多形核中性粒细胞(PMN)中溴化乙锭的掺入情况,以及通过透射电子显微镜观察PMN超微结构变化,研究了rPVL和产PVL金黄色葡萄球菌菌株粗培养上清液的细胞毒性。结果发现,IVIg可中和rPVL和金黄色葡萄球菌培养上清液的孔形成及细胞病变效应。