School of Molecular Bioscience and Bosch Institute, The University of Sydney, Sydney, Australia.
J Neuroinflammation. 2011 Sep 26;8:124. doi: 10.1186/1742-2094-8-124.
Lipocalin 2 (Lcn2) is a bacteriostatic factor that may also modulate cellular function, however, little is known concerning the expression or role of Lcn2 in CNS inflammation. Therefore, here we investigated the regulation and possible function of Lcn2 in the CNS following peripheral lipopolysaccharide (LPS) injection in mice.
A murine model for systemic endotoxemia was used in this study. Wild type or Lcn2 KO mice (both genotypes C57BL/6 strain) were given either a single or dual, staggered intraperitoneal injections of purified E. coli LPS or vehicle alone. The brain was examined for the expression and location of Lcn2 mRNA and protein and various markers for neuroinflammation were analyzed.
Although undetectable under physiological conditions, both Lcn2 mRNA and protein were induced to high levels in the brain after LPS injection. By contrast, RNA corresponding to the putative Lcn2 (termed 24p3R) receptor was present at high levels in the normal brain and remained unaltered by LPS injection. Differences between Lcn2 and 24p3R mRNA expression were found at the anatomic and cellular level. Endothelial cells, microglia and the choroid plexus but not neurons were identified as the main cellular sources for Lcn2 mRNA in the CNS. By contrast, 24p3R mRNA was detected in neurons and the choroid plexus only. Lcn2 protein was found to have a similar cellular localization as the corresponding RNA transcripts with the exception that subsets of neurons were also strongly positive. Various inflammatory, glial, and iron handling markers were analyzed and found to have similar alterations between WT and Lcn2 KO animals.
脂钙蛋白 2（Lcn2）是一种抑菌因子，也可能调节细胞功能，但关于 Lcn2 在中枢神经系统炎症中的表达或作用知之甚少。因此，本研究探讨了脂多糖（LPS）外周注射后 Lcn2 在小鼠中枢神经系统中的调节和可能功能。
本研究采用系统性内毒素血症小鼠模型。野生型或 Lcn2 KO 小鼠（均为 C57BL/6 品系）分别单次或两次 staggered 腹腔内注射纯化大肠杆菌 LPS 或单独载体。检测脑内 Lcn2 mRNA 和蛋白的表达和定位，分析各种神经炎症标志物。
尽管在生理条件下无法检测到，但 LPS 注射后 Lcn2 mRNA 和蛋白均被诱导至高水平。相比之下，正常脑内存在高表达的 Lcn2（称为 24p3R）受体的 RNA，且 LPS 注射后未改变。Lcn2 和 24p3R mRNA 表达在解剖和细胞水平上存在差异。内皮细胞、小胶质细胞和脉络丛，但不是神经元，被鉴定为中枢神经系统中 Lcn2 mRNA 的主要细胞来源。相比之下，24p3R mRNA 仅在神经元和脉络丛中检测到。Lcn2 蛋白的细胞定位与相应的 RNA 转录本相似，但部分神经元也呈强阳性。分析了各种炎症、神经胶质和铁处理标志物，发现 WT 和 Lcn2 KO 动物之间存在相似的改变。
1）LPS 系统注射强烈诱导中枢神经系统中 Lcn2 的产生，2）除了中枢神经系统中细菌进入的关键门户的 Lcn2 产生外，神经元可能是 Lcn2 作用的靶标，Lcn2 显然被这些细胞摄取，3）Lcn2 在中枢神经系统中的细胞功能仍然难以捉摸。
