Hughes Paula Marie, Botham Michelle Sandra, Frentzel Stefan, Mir Anis, Perry Victor Hugh
Nurin Ltd., CNS Inflammation Group, University of Southampton, Southampton, UK.
Glia. 2002 Mar 15;37(4):314-27.
In this study, we investigate the expression of fractalkine (CX3CL1) and the fractalkine receptor (CX3CR1) in the naive rat and mouse central nervous system (CNS). We determine if the expression of this chemokine and its receptor are altered during chronic or acute inflammation in the CNS. In addition, we determine if CX3CL1, which has been reported to be chemoattractant to leukocytes in vitro, is capable of acting as a chemoattractant in the CNS in vivo. Immunohistochemistry was performed using primary antibodies recognizing soluble and membrane-bound CX3CL1 and the N-terminus of the CX3CR1. We found that neurons in the naive rodent brain are immunoreactive for CX3CL1 and CX3CR1, both showing a perinuclear staining pattern. Resident microglia associated with the parenchyma and macrophages in the meninges and choroid plexus constituitively express CX3CR1. In a prion model of chronic neurodegeneration and inflammation, CX3CL1 immunoreactivity is upregulated in astrocytes and CX3CR1 expression is elevated on microglia. In surviving neurons, expression of CX3CL1 appears unaltered relative to normal neurons. There is a decrease in neuronal CX3CR1 expression. Acute inflammatory responses in the CNS, induced by stereotaxic injections of lipopolysaccharide or kainic acid, results in activation of microglia and astrocytes but no detectable changes in the glial expression of CX3CL1 or CX3CR1. The expression of CX3CL1 and CX3CR1 by glial cells during inflammation in the CNS may be influenced by the surrounding cytokine milieu, which has been shown to differ in acute and chronic neuroinflammation.
在本研究中，我们调查了趋化因子（CX3CL1）及其受体（CX3CR1）在未接触过抗原的大鼠和小鼠中枢神经系统（CNS）中的表达情况。我们确定了在中枢神经系统的慢性或急性炎症过程中，这种趋化因子及其受体的表达是否发生改变。此外，我们还确定了体外已报道对白细胞具有趋化作用的CX3CL1，在体内中枢神经系统中是否也能起到趋化作用。使用识别可溶性和膜结合型CX3CL1以及CX3CR1 N端的一抗进行免疫组织化学分析。我们发现，未接触过抗原的啮齿动物大脑中的神经元对CX3CL1和CX3CR1呈免疫反应性，两者均显示核周染色模式。与实质相关的常驻小胶质细胞以及脑膜和脉络丛中的巨噬细胞组成性表达CX3CR1。在慢性神经退行性变和炎症的朊病毒模型中，星形胶质细胞中CX3CL1免疫反应性上调，小胶质细胞上CX3CR1表达升高。在存活的神经元中，CX3CL1的表达相对于正常神经元似乎未发生改变。神经元CX3CR1表达有所下降。通过立体定向注射脂多糖或 kainic 酸诱导的中枢神经系统急性炎症反应，会导致小胶质细胞和星形胶质细胞活化，但胶质细胞CX3CL1或CX3CR1的表达未检测到变化。中枢神经系统炎症期间胶质细胞对CX3CL1和CX3CR1的表达可能受周围细胞因子环境的影响，急性和慢性神经炎症中的细胞因子环境已显示有所不同。
