Ginsburg I, Sadovnic M
Department of Oral Biology, Hebrew University-Hadassah, School of Dental Medicine, Jerusalem, Israel.
FEMS Immunol Med Microbiol. 1998 Nov;22(3):247-56. doi: 10.1111/j.1574-695X.1998.tb01213.x.
An in vitro model was employed to study the potential role of streptococcal extra-cellular products, rich in streptolysin O, in cellular injury as related to streptococcal infections and post-streptococcal sequelae. Extra-cellular products (EXPA) rich in streptolysin O were isolated from type 4, group A hemolytic streptococci grown in a chemostat, in a synthetic medium. EXPA induced moderate cytopathogenic changes in monkey kidney epithelial cells and in rat heart cells pre-labeled with 3H-arachidonate. However very strong toxic effects were induced when EXP was combined with oxidants (glucose oxides generated H2O2, AAPH-induced peroxyl radical (ROO.), NO generated by sodium nitroprusside) and proteinases (plasmin, trypsin). Cell killing was distinctly synergistic in nature. Cell damage induced by the multi-component cocktails was strongly inhibited either by micromolar amounts of gamma globulin, and Evan's blue which neutralized SLO activity, by tetracycline, trasylol (aprotinin), epsilon amino caproic acid and by soybean trypsin inhibitor, all proteinase inhibitors as well as by a non-penetrating PLA2 inhibitor A. The results suggest that fasciitis, myositis and sepsis resulting from infections with hemolytic streptococci might be caused by a coordinated 'cross-talk' among microbial, leukocyte and additional host-derived pro-inflammatory agents. Since attempts to prolong lives of septic patients by the exclusive administration of single antagonists invariably failed, it is proposed that the administration of 'cocktails' of putative inhibitors against major pro-inflammatory agonizes generated in inflammation and infection might protect against the deleterious effects caused by the biochemical and pharmacological cascades which are known to be activated in sepsis.
采用体外模型研究富含链球菌溶血素O的链球菌细胞外产物在与链球菌感染及链球菌感染后后遗症相关的细胞损伤中的潜在作用。从在恒化器中于合成培养基中培养的4型A组溶血性链球菌中分离出富含链球菌溶血素O的细胞外产物（EXPA）。EXPA在猴肾上皮细胞和预先用3H-花生四烯酸标记的大鼠心脏细胞中诱导了中度细胞病变变化。然而，当EXPA与氧化剂（葡萄糖氧化酶产生的H2O2、AAPH诱导的过氧自由基（ROO.）、硝普钠产生的NO）和蛋白酶（纤溶酶、胰蛋白酶）结合时，会诱导非常强烈的毒性作用。细胞杀伤本质上具有明显的协同作用。由多组分混合物诱导的细胞损伤可被微摩尔量的γ球蛋白、中和SLO活性的伊文思蓝、四环素、抑肽酶（抑蛋白酶肽）、ε-氨基己酸和大豆胰蛋白酶抑制剂（所有蛋白酶抑制剂）以及非穿透性PLA2抑制剂A强烈抑制。结果表明，溶血性链球菌感染引起的筋膜炎、肌炎和败血症可能是由微生物、白细胞和其他宿主来源的促炎剂之间协调的“串扰”所致。由于仅使用单一拮抗剂来延长败血症患者生命的尝试总是失败，因此有人提出，针对炎症和感染中产生的主要促炎激动剂给予假定抑制剂的“鸡尾酒”可能会保护机体免受已知在败血症中被激活的生化和药理级联反应所造成的有害影响。
