Red Blood Cell Susceptibility to Pneumolysin CORRELATION WITH MEMBRANE BIOCHEMICAL AND PHYSICAL PROPERTIES
Red Blood Cell Susceptibility to Pneumolysin CORRELATION WITH MEMBRANE BIOCHEMICAL AND PHYSICAL PROPERTIES
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DOI：
10.1074/jbc.m115.691899
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发表时间：
2016-05-06
影响因子：
4.8
通讯作者：
Winlove, C. Peter
中科院分区：
文献类型：
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作者：
Bokori-Brown, Monika;Petrov, Peter G.;Winlove, C. Peter
本研究通过单细胞研究，探讨了质膜的生化和生物物理特性以及膜形态对人红细胞对肺炎链球菌关键毒力因子胆固醇依赖性溶血素（cytolyysin pneumolyysin）敏感性的影响。我们展示了膜的物理性质（弯曲刚度、表面和偶极子静电电位）与红细胞对溶血素诱导的溶血的敏感性之间的相关性。我们证明由氧化应激、脂质混乱和人工细胞老化引起的膜的生化修饰可调节细胞对毒素的反应。我们提供的证据表明，糖尿病红细胞对溶血素的反应多样性与糖化血红蛋白水平相关，并且糖尿病患者红细胞质膜的机械特性发生改变。最后，我们发现与健康红细胞相比，糖尿病红细胞对溶血素和相关毒素溶血素O的抵抗力更强。综上所述，这些研究表明，在人类红细胞群体中，细胞对溶血素反应的多样性受到质膜的生物物理和生化状态以及细胞的化学和/或氧化应激历史的影响。
This study investigated the effect of the biochemical and biophysical properties of the plasma membrane as well as membrane morphology on the susceptibility of human red blood cells to the cholesterol-dependent cytolysin pneumolysin, a key virulence factor of Streptococcus pneumoniae, using single cell studies. We show a correlation between the physical properties of the membrane (bending rigidity and surface and dipole electrostatic potentials) and the susceptibility of red blood cells to pneumolysin-induced hemolysis. We demonstrate that biochemical modifications of the membrane induced by oxidative stress, lipid scrambling, and artificial cell aging modulate the cell response to the toxin. We provide evidence that the diversity of response to pneumolysin in diabetic red blood cells correlates with levels of glycated hemoglobin and that the mechanical properties of the red blood cell plasma membrane are altered in diabetes. Finally, we show that diabetic red blood cells are more resistant to pneumolysin and the related toxin perfringolysin O relative to healthy red blood cells. Taken together, these studies indicate that the diversity of cell response to pneumolysin within a population of human red blood cells is influenced by the biophysical and biochemical status of the plasma membrane and the chemical and/or oxidative stress pre-history of the cell.