A Homologous form of Human Interleukin 16 is Implicated in Microglia Recruitment Following Nervous System Injury in Leech Hirudo medicinalis
A Homologous form of Human Interleukin 16 is Implicated in Microglia Recruitment Following Nervous System Injury in Leech Hirudo medicinalis
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DOI：
10.1002/glia.21036
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发表时间：
2010-11-01
期刊：
影响因子：
6.2
通讯作者：
Lefebvre, Christophe
中科院分区：
文献类型：
--
作者：
Croq, Francoise;Vizioli, Jacopo;Lefebvre, Christophe
与哺乳动物不同的是，药用水蛭水蛭可以在损伤后完全修复其中枢神经系统（CNS）。这种无脊椎动物模型为研究CNS修复过程的分子和细胞基础提供了独特的机会。当水蛭中枢神经系统受损时，小胶质细胞迁移并聚集在病变部位，这是一种已知对于受损轴突通常发芽至关重要的现象。在本研究中，我们证明了一种新的分子，命名为HmIL-16，与人白细胞介素-16（IL-16）具有功能同源性，具有水蛭小胶质细胞的趋化活性，观察使用梯度的人IL-16。用抗人IL-16抗体或抗HmIL-16抗体预孵育小胶质细胞显著降低水蛭条件培养基诱导的小胶质细胞迁移。通过HmIL-16促进人CD 4 + T细胞迁移的能力进一步证明了功能同源性，该能力被针对人IL-16的抗体、IL-16拮抗剂肽或可溶性CD 4抑制。水蛭CNS的免疫组化结果表明，神经元中存在的HmIL-16蛋白被迅速运输并沿着轴突突起储存，以促进小胶质细胞向受损轴突的募集。据我们所知，这是第一次在无脊椎动物中枢神经系统中鉴定出功能性白细胞介素-16同源物。HmIL-16将小胶质细胞募集到CNS损伤部位的能力表明HmIL-16在水蛭CNS修复中神经元和小胶质细胞之间的串扰中的作用。(C)2010 Wiley-Liss，Inc.
In contrast to mammals, the medicinal leech Hirudo medicinalis can completely repair its central nervous system (CNS) after injury. This invertebrate model offers unique opportunities to study the molecular and cellular basis of the CNS repair processes. When the leech CNS is injured, microglial cells migrate and accumulate at the site of lesion, a phenomenon known to be essential for the usual sprouting of injured axons. In the present study, we demonstrate that a new molecule, designated HmIL-16, having functional homologies with human interleukin-16 (IL-16), has chemotactic activity on leech microglial cells as observed using a gradient of human IL-16. Preincubation of microglial cells either with an anti-human IL-16 antibody or with anti-HmIL-16 antibody significantly reduced microglia migration induced by leech-conditioned medium. Functional homology was demonstrated further by the ability of HmIL-16 to promote human CD4+ T cell migration which was inhibited by antibody against human IL-16, an IL-16 antagonist peptide or soluble CD4. Immunohistochemistry of leech CNS indicates that HmIL-16 protein present in the neurons is rapidly transported and stored along the axonal processes to promote the recruitment of microglial cells to the injured axons. To our knowledge, this is the first identification of a functional interleukin-16 homologue in invertebrate CNS. The ability of HmIL-16 to recruit microglial cells to sites of CNS injury suggests a role for HmIL-16 in the crosstalk between neurons and microglia in the leech CNS repair. (C) 2010 Wiley-Liss, Inc.