Katychev Andre, Wang Xueqain, Duffy Alexandra, Dore-Duffy Paula
Multiple Sclerosis Clinical Research Center, Department of Neurology, Division of Neuroimmunology, Wayne State University School of Medicine, Detroit Medical Center, Detroit, Mich. 48201, USA.
Dev Neurosci. 2003 Nov-Dec;25(6):436-46. doi: 10.1159/000075669.
Pericyte loss or migration from its vascular location may be an important step in microvascular remodeling. Decreased pericyte to endothelial ratios are characteristics of newly formed vessels as well as microvessels undergoing regression, and may be due to selective degeneration via necrotic cell death or via programmed cell death. In this study, we have examined glucocorticoid-induced apoptosis in primary rat CNS pericytes. Characterization of apoptosis was determined using five independent criteria: (1) the translocation of receptors for annexin V from the inner to the outer surface of the plasma membrane, (2) the translocation of cytochrome C from the mitochondria to the cytosol, (3) the induction of DNA fragmentation, (4) the induction of classic changes in cell morphology, and (5) the appearance of TUNEL-positive cells. Incubation of CNS pericytes with dexamethasone induced the appearance of apoptotic cells in a time- and dose-dependent manner. Pericytes express immunologically detectable glucocorticoid receptors, and addition of the glucocorticoid receptor antagonist mifepristone inhibited dexamethasone-induced pericyte apoptosis. That pericytes undergo apoptosis in response to dexamethasone suggests that the regulatory function of this steroid may be important in vascular development and that pericyte apoptotic cell death may accompany vascular regression. Deregulation of pericyte involvement in vascular homeostasis and hemostasis may result in clinical disease.
周细胞从其血管位置丢失或迁移可能是微血管重塑的重要步骤。周细胞与内皮细胞比例降低是新生血管以及正在消退的微血管的特征，可能是由于坏死性细胞死亡或程序性细胞死亡导致的选择性退化。在本研究中，我们检测了糖皮质激素诱导的原代大鼠中枢神经系统周细胞凋亡。使用五个独立标准确定凋亡特征：（1）膜联蛋白V受体从质膜内表面向外表面的转位；（2）细胞色素C从线粒体向细胞质的转位；（3）DNA片段化的诱导；（4）细胞形态经典变化的诱导；（5）TUNEL阳性细胞的出现。用 dexamethasone 孵育中枢神经系统周细胞以时间和剂量依赖性方式诱导凋亡细胞的出现。周细胞表达免疫可检测的糖皮质激素受体，添加糖皮质激素受体拮抗剂米非司酮可抑制 dexamethasone 诱导的周细胞凋亡。周细胞对 dexamethasone 产生凋亡表明该类固醇的调节功能在血管发育中可能很重要，并且周细胞凋亡性细胞死亡可能伴随血管消退。周细胞参与血管稳态和止血的失调可能导致临床疾病。
