Glycerol Monolaurate Inhibits the Effects of Gram-Positive Select Agents on Eukaryotic Cells
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- 作者：Marnie L. Peterson and Patrick M. Schlievert
- 刊名：Biochemistry
- 出版年：2006
- 出版时间：February 21, 2006
- 年：2006
- 卷：45
- 期：7
- 页码：2387 - 2397
- 全文大小：95K
- 年卷期：v.45,no.7(February 21, 2006)
- ISSN：1520-4995
文摘
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 arebioterrorism 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-positivebacterial exotoxins. This study explored the ability of GML to inhibit the effects of exotoxins on mammaliancells and prevent rabbit lethality from TSS. GML (
10 
g/mL) inhibited superantigen (5 g/mL)immunoproliferation, as determined by inhibition of 3H-thymidine incorporation into DNA of humanperipheral blood mononuclear cells (1 × 106 cells/mL) as well as phospholipase C
1, suggesting inhibitionof signal transduction. The compound (20 g/mL) prevented superantigen (100 g/mL) induced cytokinesecretion by human vaginal epithelial cells (HVECs) as measured by ELISA. GML (250 g) inhibitedrabbit lethality as a result of TSST-1 administered vaginally. GML (10 g/mL) inhibited HVEC andmacrophage cytotoxicity by anthrax toxin, prevented erythrocyte lysis by purified hemolysins (staphylococcal 
and 
) and culture fluids containing streptococcal and Bacillus anthracis hemolysins, and wasnontoxic to mammalian cells (up to 100 g/mL) and rabbits (250 g). GML stabilized mammalian cellmembranes, because erythrocyte lysis was reduced in the presence of hypotonic aqueous solutions (0-0.05 M saline) or staphylococcal - and -hemolysins when erythrocytes were pretreated with GML.GML may be useful in the management of Gram-positive exotoxin illnesses; its action appears to bemembrane stabilization with inhibition of signal transduction.
10 g/mL) inhibited superantigen (5 g/mL)immunoproliferation, as determined by inhibition of 3H-thymidine incorporation into DNA of humanperipheral blood mononuclear cells (1 × 106 cells/mL) as well as phospholipase C1, suggesting inhibitionof signal transduction. The compound (20 g/mL) prevented superantigen (100 g/mL) induced cytokinesecretion by human vaginal epithelial cells (HVECs) as measured by ELISA. GML (250 g) inhibitedrabbit lethality as a result of TSST-1 administered vaginally. GML (10 g/mL) inhibited HVEC andmacrophage cytotoxicity by anthrax toxin, prevented erythrocyte lysis by purified hemolysins (staphylococcal and ) and culture fluids containing streptococcal and Bacillus anthracis hemolysins, and wasnontoxic to mammalian cells (up to 100 g/mL) and rabbits (250 g). GML stabilized mammalian cellmembranes, because erythrocyte lysis was reduced in the presence of hypotonic aqueous solutions (0-0.05 M saline) or staphylococcal - and -hemolysins when erythrocytes were pretreated with GML.GML may be useful in the management of Gram-positive exotoxin illnesses; its action appears to bemembrane stabilization with inhibition of signal transduction.