DFG Membrane/Cytoskeleton Interaction Group, Institute of Pharmacology and Toxicology & Rudolf Virchow Center for Experimental Medicine, University of Würzburg, Versbacherstr. 9, 97078 Würzburg, Germany.
Glia. 2012 Jan;60(1):137-46. doi: 10.1002/glia.21256. Epub 2011 Oct 11.
Astrocytes represent a major component of brain tissue and play a critical role in the proper functioning and protection of the brain. Streptococcus pneumoniae, the most common cause of bacterial meningitis, has a high lethality and causes serious disabilities in survivors. Pneumolysin (PLY), a member of the cholesterol-dependent cytolysin group and a major S. pneumoniae neurotoxin, causes deterioration over the course of experimental S. pneumoniae meningitis. At disease-relevant sub-lytic concentrations, PLY produces actin and tubulin reorganization and astrocyte cell shape changes in vitro. In this article, we show that sub-lytic amounts of PLY remodel brain tissue and produce astrocytic process retraction, cortical astroglial reorganization and increased interstitial fluid retention, which is manifested as tissue edema. These changes caused increased tissue permeability to macromolecules and bacteria. The pore-forming capacity of PLY remained necessary for these changes because none of the nonpore-forming mutants were capable of producing similar effects. We suggest that PLY can increase the permeability of brain tissue toward pathogenic factors and bacteria in the course of meningitis, thus contributing to the deterioration caused by the disease.
星形胶质细胞是脑组织的主要组成部分，在大脑的正常功能和保护中起着关键作用。肺炎链球菌是细菌性脑膜炎最常见的病因，其致死率高，幸存者会出现严重残疾。肺炎球菌溶血素（PLY）是胆固醇依赖性细胞溶解素家族的成员，也是主要的肺炎球菌神经毒素，在实验性肺炎球菌性脑膜炎的发展过程中会导致病情恶化。在与疾病相关的亚致死浓度下，PLY 会导致体外肌动蛋白和微管重排以及星形胶质细胞形态变化。在本文中，我们表明，PLY 的亚致死量会重塑脑组织并导致星形胶质细胞突起回缩、皮质星形胶质细胞重组和细胞外间隙液体潴留增加，表现为组织水肿。这些变化导致组织对大分子和细菌的通透性增加。PLY 的成孔能力对于这些变化仍然是必要的，因为没有一种非成孔突变体能够产生类似的效果。我们认为，在脑膜炎过程中，PLY 可以增加脑组织对致病因子和细菌的通透性，从而导致疾病的恶化。
