Yamate J, Ishimine S, Izawa T, Kumagai D, Kuwamura M
Laboratory of Veterinary Pathology, Life and Environmental Sciences, Osaka Prefecture University, Nakaku, Sakai, Osaka, Japan.
Histol Histopathol. 2009 Jan;24(1):13-24. doi: 10.14670/HH-24.13.
Macrophages play important roles in host defense mechanisms. In the brain, besides microglial cells, meningeal macrophages are present. However, the pathobiological characteristics of meningeal macrophages in rats remain to be investigated. In normal meninx, immunohistochemically, macrophages reacting to CD163 (macrophage scavenger receptor) and major histocompatibility complex (MHC) class II-expressing cells (involving activated macrophages or dendritic cells) were sporadically seen without age-dependent changes. Injection of lipoplysaccharide (LPS) (5 microg; Escherichia coli) into the cerebrum increased the number of anti-CD68-positive macrophages (with greater phagocytic activity) in the meninx, with a peak at 12 h during observation period until 48 h; MHC class II-expressing cells showed a gradual increase in number from 3 h after injection; however, anti-CD163-positive macrophages did not show significant change. In in vitro studies, LPS (0, 0.02, 0.05, 0.5, 5, 50 and 100 microg/ml) was added to KMY-1 or KMY-2 cells, both of which had been established from a rat malignant meningioma. KMY-1 originally reacted to CD163, but LPS addition at 0.5 microg/ml and greater concentrations decreased the anti-CD163-positive cell number and instead increased the anti-CD68-positive cell number. LPS-treated KMY-2 increased the anti-CD163-positive cell number at 0.05 and 0.5 microg/ml. By RT-PCR methods, LPS (0, 0.5, 5, 50, and 100 microg/ml)-treated KMY-1 and KMY-2 showed an increase in mRNA of monocyte chemoattractant protein-1 (MCP-1, a chemokine), and LPS-treated KMY-2 increased mRNA of nerve growth factor (NGF, an immunological effecter). Collectively, under LPS treatment, macrophages with heterogeneous functions appear in rat meninx; rat meninx-forming cells may be involved in pathogenesis of meningeal inflammation by expressing different immunophenotypes and by producing regulatory proinflammatory factors such as MCP-1 and NGF.
巨噬细胞在宿主防御机制中发挥着重要作用。在大脑中，除了小胶质细胞外，还存在脑膜巨噬细胞。然而，大鼠脑膜巨噬细胞的病理生物学特征仍有待研究。在正常脑膜中，免疫组织化学显示，对CD163（巨噬细胞清道夫受体）有反应的巨噬细胞和表达主要组织相容性复合体（MHC）II类的细胞（包括活化的巨噬细胞或树突状细胞）偶尔可见，且无年龄依赖性变化。向大脑注射脂多糖（LPS，5微克；大肠杆菌）可增加脑膜中抗CD68阳性巨噬细胞（吞噬活性更强）的数量，在观察期48小时内，12小时时达到峰值；表达MHC II类的细胞数量从注射后3小时开始逐渐增加；然而，抗CD163阳性巨噬细胞数量没有显著变化。在体外研究中，将LPS（0、0.02、0.05、0.5、5、50和100微克/毫升）添加到KMY-1或KMY-2细胞中，这两种细胞均源自大鼠恶性脑膜瘤。KMY-1原本对CD163有反应，但添加0.5微克/毫升及更高浓度的LPS会减少抗CD163阳性细胞数量，反而增加抗CD68阳性细胞数量。用LPS处理的KMY-2在0.05和0.5微克/毫升时抗CD163阳性细胞数量增加。通过逆转录聚合酶链反应（RT-PCR）方法，用LPS（0、0.5、5、50和100微克/毫升）处理的KMY-1和KMY-2显示单核细胞趋化蛋白-1（MCP-1，一种趋化因子）的信使核糖核酸（mRNA）增加，用LPS处理的KMY-2神经生长因子（NGF，一种免疫效应因子）的mRNA增加。总体而言，在LPS处理下，大鼠脑膜中会出现功能异质性的巨噬细胞；大鼠脑膜形成细胞可能通过表达不同的免疫表型以及产生调节性促炎因子如MCP-1和NGF参与脑膜炎症的发病机制。
