Brandenburg Lars-Ove, Varoga Deike, Nicolaeva Nicoletta, Leib Stephen L, Podschun Rainer, Wruck Christoph J, Wilms Henrik, Lucius Ralph, Pufe Thomas
Department of Anatomy and Cell Biology, RWTH Aachen University, Germany.
J Neuroimmunol. 2009 Dec 10;217(1-2):55-64. doi: 10.1016/j.jneuroim.2009.10.004. Epub 2009 Oct 30.
Bacterial meningitis is characterized by an inflammation of the meninges and continues to be an important cause of mortality and morbidity. Meningeal cells cover the cerebral surface and are involved in the first interaction between pathogens and the brain. Little is known about the role of meningeal cells and the expression of antimicrobial peptides in the innate immune system. In this study we characterized the expression, secretion and bactericidal properties of rat cathelin-related antimicrobial peptide (rCRAMP), a homologue of the human LL-37, in rat meningeal cells after incubation with different bacterial supernatants and the bacterial cell wall components lipopolysaccharide (LPS) and peptidoglycan (PGN). Using an agar diffusion test, we observed that supernatants from meningeal cells incubated with bacterial supernatants, LPS and PGN showed signs of antimicrobial activity. The inhibition of rCRAMP expression using siRNA reduced the antimicrobial activity of the cell culture supernatants. The expression of rCRAMP in rat meningeal cells involved various signal transduction pathways and was induced by the inflammatory cytokines interleukin-1, -6 and tumor necrosis factor alpha. In an experimental model of meningitis, infant rats were intracisternally infected with Streptococcus pneumoniae and rCRAMP was localized in meningeal cells using immunohistochemistry. These results suggest that cathelicidins produced by meningeal cells play an important part in the innate immune response against pathogens in CNS bacterial infections.
细菌性脑膜炎的特征是脑膜炎症，仍然是死亡率和发病率的重要原因。脑膜细胞覆盖大脑表面，参与病原体与大脑之间的首次相互作用。关于脑膜细胞的作用以及抗菌肽在先天免疫系统中的表达，人们了解甚少。在本研究中，我们对大鼠与人类LL-37同源的cathelin相关抗菌肽（rCRAMP）在与不同细菌上清液以及细菌细胞壁成分脂多糖（LPS）和肽聚糖（PGN）孵育后的大鼠脑膜细胞中的表达、分泌和杀菌特性进行了表征。使用琼脂扩散试验，我们观察到与细菌上清液、LPS和PGN孵育的脑膜细胞上清液显示出抗菌活性迹象。使用小干扰RNA（siRNA）抑制rCRAMP表达降低了细胞培养上清液的抗菌活性。rCRAMP在大鼠脑膜细胞中的表达涉及多种信号转导途径，并由炎性细胞因子白细胞介素-1、-6和肿瘤坏死因子α诱导。在脑膜炎实验模型中，幼鼠经脑池内感染肺炎链球菌，并使用免疫组织化学方法将rCRAMP定位在脑膜细胞中。这些结果表明，脑膜细胞产生的cathelicidins在中枢神经系统细菌感染中针对病原体的先天免疫反应中起重要作用。
