Petrushanko I Y, Melnikova E V, Yurinskaya M M, Vinokurov M G, Suslikov A V, Mitkevich V A, Makarov A A
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia.
Mol Biol (Mosk). 2019 Jan-Feb;53(1):101-108. doi: 10.1134/S0026898419010130.
Lipopolysaccharides (LPS), components of the cell wall of gram-negative bacteria, activate neutrophils that trigger pathological processes, including gram-negative sepsis. LPS inhibit spontaneous apoptosis of neutrophils that leads to inflammation. In this work we tested the action of H2S donor (GYY4137) on the activation of human neutrophils by E. coli LPS. We estimated the changes in redox status (ROS level, intracellularglutathione, NO), apoptosis and mitochondrial potential of neutrophils under the LPS action in the presence and absence of GYY4137. GYY4137 reduces the ROS level, slightly reduces GSH, does not influence the NO level and has no apoptogenic effect. LPS induce the increasing of ROS level and inhibit spontaneous apoptosis of neutrophils. We found that GYY4137 prevents the growth of ROS caused by LPS and leads to a reduction of LPS-induced inhibition of neutrophil apoptosis. Thus the mechanism of GYY4137 protection against inflammation, triggered by bacterial infection, is concerned with the neutralization of LPS effect on neutrophils.
脂多糖(LPS)是革兰氏阴性菌细胞壁的组成成分,可激活中性粒细胞,引发包括革兰氏阴性菌败血症在内的病理过程。LPS抑制中性粒细胞的自发凋亡,从而导致炎症。在本研究中,我们测试了硫化氢供体(GYY4137)对大肠杆菌LPS激活人中性粒细胞的作用。我们评估了在存在和不存在GYY4137的情况下,LPS作用下中性粒细胞的氧化还原状态(ROS水平、细胞内谷胱甘肽、NO)、凋亡和线粒体电位的变化。GYY4137可降低ROS水平,轻微降低谷胱甘肽水平,不影响NO水平,且无凋亡诱导作用。LPS可诱导ROS水平升高并抑制中性粒细胞的自发凋亡。我们发现,GYY4137可阻止LPS引起的ROS增长,并导致LPS诱导的中性粒细胞凋亡抑制作用减弱。因此,GYY4137预防细菌感染引发炎症的机制与中和LPS对中性粒细胞的作用有关。