Glycerol monolaurate inhibits the effects of gram-positive select agents on eukaryotic cells
Glycerol monolaurate inhibits the effects of gram-positive select agents on eukaryotic cells
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DOI：
10.1021/bi051992u
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发表时间：
2006-02-21
期刊：
影响因子：
2.9
通讯作者：
Schlievert, PM
中科院分区：
文献类型：
--
作者：
Peterson, ML;Schlievert, PM
革兰氏阳性菌的许多外毒素，如超级抗原[葡萄球菌肠毒素，中毒性休克综合征毒素-1 (TSST-1)，链球菌热原外毒素]和炭疽毒素是通过免疫刺激或细胞毒性引起疾病的生物恐怖剂。甘油单月桂酸酯（GML）是一种天然存在于人体内的脂肪酸单酯，据报道可以防止革兰氏阳性细菌外毒素的合成。本研究探讨了GML抑制外毒素对哺乳动物细胞的影响，防止家兔TSS致死性的能力。GML （>= 10 μ g/mL）抑制超抗原（5 μ g/mL）的免疫增殖，通过抑制人外周血单个核细胞（1 × 10(6)个细胞/mL） DNA中h -3胸腺嘧啶的掺入以及磷脂酶C γ 1来确定，提示其抑制信号转导。ELISA检测该化合物（20 μ g/mL）对超抗原（100 μ g/mL）诱导的人阴道上皮细胞（HVECs）分泌细胞因子有抑制作用。GML （250 μ g）对家兔TSST-1致死性有抑制作用。管理,阴道分娩。GML （10 μ g/mL）抑制炭疽毒素对HVEC和巨噬细胞的细胞毒性，抑制纯化溶血素（葡萄球菌α和）和含有链球菌和炭疽芽孢杆菌溶血素的培养液对红细胞的溶解，对哺乳动物细胞（LIP至100 μ g/mL）和家兔（250 μ g）无毒。GML稳定了哺乳动物细胞膜，因为当红细胞用GML预处理时，低渗水溶液（0-0.05 M生理盐水）或葡萄球菌α和β溶血素存在时，红细胞溶解减少。GML可能对革兰氏阳性外毒素疾病的治疗有用；它的作用似乎是抑制信号转导的膜稳定。
Many exotoxins of Gram-positive bacteria, such as superantigens [staphylococcal enterotoxins, toxic shock syndrome toxin-1 (TSST-1), and streptococcal pyrogenic exotoxins] and anthrax toxin are bioterrorism agents that cause diseases by immunostimulation or cytotoxicity. Glycerol monolaurate (GML), a fatty acid monoester found naturally in humans, has been reported to prevent synthesis of Gram-positive bacterial exotoxins. This study explored the ability of GML to inhibit the effects of exotoxins on mammalian cells and prevent rabbit lethality from TSS. GML (>= 10 mu g/mL) inhibited superantigen (5 mu g/mL) immunoproliferation, as determined by inhibition of H-3-thymidine incorporation into DNA of human peripheral blood mononuclear cells (1 X 10(6) cells/mL) as well as phospholipase C gamma 1, suggesting inhibition of signal transduction. The compound (20 mu g/mL) prevented superantigen (100 mu g/mL) induced cytokine secretion by human vaginal epithelial cells (HVECs) as measured by ELISA. GML (250 mu g) inhibited rabbit lethality as a result of TSST-1. administered vaginally. GML (10 mu g/mL) inhibited HVEC and macrophage cytotoxicity by anthrax toxin, prevented erythrocyte lysis by purified hemolysins (staphylococcal alpha and) and culture fluids containing streptococcal and Bacillus anthracis hemolysins, and was nontoxic to mammalian cells (LIP to 100 mu g/mL) and rabbits (250 mu g). GML stabilized mammalian cell membranes, because erythrocyte lysis was reduced in the presence of hypotonic aqueous solutions (0-0.05 M saline) or staphylococcal alpha- and beta-hemolysins when erythrocytes were pretreated with GML. GML may be useful in the management of Gram-positive exotoxin illnesses; its action appears to be membrane stabilization with inhibition of signal transduction.