Gordon Renee J, McGregor Ailsa L, Connor Bronwen
Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Mol Cell Neurosci. 2009 Jun;41(2):219-32. doi: 10.1016/j.mcn.2009.03.001. Epub 2009 Mar 28.
In this study we demonstrate the chemokines MCP-1, MIP-1alpha and GRO-alpha play a role in directing adult subventricular zone (SVZ)-derived progenitor cell migration following striatal cell death. MCP-1, MIP-1alpha and GRO-alpha were significantly upregulated in the striatum 2-3 days following QA-induced lesioning, correlating with maximum SVZ-derived progenitor cell recruitment into the lesioned striatum. We established that SVZ-derived progenitor cells express receptors for each chemokine, and demonstrated MCP-1, MIP-1alpha and GRO-alpha to be potent chemoattractants for SVZ-derived progenitor cells in vitro. Immunofluorescence revealed MCP-1, MIP-1alpha and GRO-alpha are predominantly expressed in the striatum by NG2-positive cells that appear to infiltrate from the bloodstream 6 h following QA lesioning. These results indicate that upregulation of MCP-1, MIP-1alpha and GRO-alpha following striatal cell death leads to chemoattraction of SVZ-derived progenitor cells into the damaged striatum and raises a potential role for blood-derived cells in directing the recruitment of SVZ-derived progenitors following brain injury.
在本研究中，我们证明趋化因子MCP-1、MIP-1α和GRO-α在纹状体细胞死亡后引导成年脑室下区（SVZ）来源的祖细胞迁移中发挥作用。在喹啉酸（QA）诱导损伤后2-3天，纹状体中MCP-1、MIP-1α和GRO-α显著上调，这与SVZ来源的祖细胞向损伤纹状体的最大募集相关。我们证实SVZ来源的祖细胞表达每种趋化因子的受体，并证明MCP-1、MIP-1α和GRO-α在体外是SVZ来源祖细胞的有效趋化剂。免疫荧光显示，MCP-1、MIP-1α和GRO-α主要由QA损伤后6小时似乎从血流中浸润的NG2阳性细胞在纹状体中表达。这些结果表明，纹状体细胞死亡后MCP-1、MIP-1α和GRO-α的上调导致SVZ来源的祖细胞向受损纹状体的化学吸引，并提出了血液来源细胞在脑损伤后引导SVZ来源祖细胞募集方面的潜在作用。
