Wu Chun-Yun, Kaur Charanjit, Lu Jia, Cao Qiong, Guo Chun-Hua, Zhou Yan, Sivakumar Viswanathan, Ling Eng-Ang
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Glia. 2006 Nov 1;54(6):513-25. doi: 10.1002/glia.20402.
Amoeboid microglial cells (AMC) which transiently exist in the corpus callosum in the postnatal rat brain expressed endothelins (ETs), specifically endothelin-1 (ET-1) and ET3 as revealed by real time RT-PCR. ET immunoreactive AMC occurred in large numbers at birth, but were progressively reduced with age and were undetected in 14 days. In rats subjected to hypoxia exposure, ET immunoexpression in AMC was reduced but the incidence of apoptotic cells was not increased when compared with the control suggesting that this was due to its downregulation that may help regulate the constriction of blood vessels bearing ET-A receptor. AMC were endowed ET-B receptor indicating that ET released by the cells may also act via an autocrine manner. In microglia activated by lipopolysaccharide (LPS), ET-1 mNA expression coupled with that of monocyte chemoattractant protein (MCP-1) and stromal derived factor-1 (SDF-1) was markedly increased; ET-3 mRNA, however, remained unaffected. AMC exposed to oxygen glucose deprivation (OGD) in vitro resulted in increase in both ET-1 and ET-3 mRNA expression. It is suggested that the downregulated ETs expression in vivo of AMC subjected to hypoxia as opposed to its upregulated expression in vitro may be due to the complexity of the brain tissue. Furthermore, the differential ET-1 and ET-3 mRNA expression in LPS and OGD treatments may be due to different signaling pathways independently regulating the two isoforms. The present novel finding has added microglia as a new cellular source of ET that may take part in multiple functions including regulating vascular constriction and chemokines release.
变形小胶质细胞（AMC）短暂存在于新生大鼠脑胼胝体中，实时逆转录聚合酶链反应显示其表达内皮素（ETs），尤其是内皮素-1（ET-1）和ET3。出生时大量出现ET免疫反应性AMC，但随年龄增长逐渐减少，14天时未检测到。与对照组相比，缺氧暴露大鼠中，AMC的ET免疫表达降低，但凋亡细胞发生率未增加，提示这是由于其下调可能有助于调节携带ET-A受体的血管收缩。AMC具有ET-B受体，表明细胞释放的ET也可能通过自分泌方式起作用。在脂多糖（LPS）激活的小胶质细胞中，ET-1 mRNA表达与单核细胞趋化蛋白（MCP-1）和基质衍生因子-1（SDF-1）的表达显著增加；然而，ET-3 mRNA不受影响。体外暴露于氧葡萄糖剥夺（OGD）的AMC导致ET-1和ET-3 mRNA表达均增加。提示缺氧的AMC在体内ETs表达下调，与其在体外上调表达相反，可能是由于脑组织的复杂性。此外，LPS和OGD处理中ET-1和ET-3 mRNA表达的差异可能是由于不同的信号通路独立调节这两种异构体。目前这一新颖发现增加了小胶质细胞作为ET的新细胞来源，其可能参与包括调节血管收缩和趋化因子释放在内的多种功能。
