Expression of JE (Monocyte chemoattractant protein-1) is induced by sciatic axotomy in wild type rodents but not in C57BL/Wlds mice
Expression of JE (Monocyte chemoattractant protein-1) is induced by sciatic axotomy in wild type rodents but not in C57BL/Wlds mice
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DOI：
10.1097/00005072-199810000-00004
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发表时间：
1998-10-01
影响因子：
3.2
通讯作者：
Frohnert, PW
中科院分区：
文献类型：
--
作者：
Carroll, SL;Frohnert, PW
血源性骨髓单核细胞募集到损伤的周围神经是轴突再生所必需的。单核细胞趋化蛋白-1（JE）和黑色素瘤生长刺激活性/gro（KC）“立即早期”基因产物在此过程中可能很重要，因为这些蛋白质分别是巨噬细胞和中性粒细胞的强效趋化剂。为了验证这一假设，我们研究了手术切断后0-30天大鼠坐骨神经中的JE和KC激活。JE和KC表达的RT-PCR和原位杂交分析表明，这些mRNA存在于损伤的神经中，在损伤后1.5小时首先由创伤区域内的细胞亚群表达。横切后16小时，在近端残端和整个远端神经节段中发现JE阳性神经内膜细胞亚群，损伤后1天出现最大mRNA积累，表达持续到切开后18天，这是巨噬细胞浸润的前一段时间。相比之下，在切开术后3天，KC表达显著减少，这与对神经损伤的有限的嗜酸性反应一致。还在C57 BL/Wld（s）小鼠及其亲本C57 BL/6 J品系中检查了JE表达，所述小鼠具有与巨噬细胞募集失败相关的延迟沃勒变性。虽然JE mRNA在C57 BL/6 J小鼠的坐骨神经中是可诱导的，但这些转录物在C57 BL/Wld（s）小鼠的损伤神经中是检测不到的。我们的研究结果表明，激活的JE位点是至少部分负责巨噬细胞入侵受伤的外周神经。此外，C57 BL/Wld（s）小鼠中有缺陷的切开术后巨噬细胞募集可能涉及JE诱导失败。
Recruitment of hematogenous myelomonocytic cells into injured peripheral nerve is essential for axonal regeneration. The monocyte chemoattractant protein-1 (JE) and melanoma growth stimulatory activity/gro (KC) "immediate early" gene products may be important in this process as these proteins are potent chemoattractants for macrophages and neutrophils, respectively. To test this hypothesis, we examined JE and KC activation in rat sciatic nerve 0-30 days after surgical transection. RT-PCR and in situ hybridization analyses of JE and KC expression demonstrates these mRNAs are present in injured nerve, first being expressed by a cellular subpopulation within the zone of trauma by 1.5 hours after injury. By 16 hours post-transection a subpopulation of JE-positive endoneurial cells is found in the proximal stump and throughout the distal nerve segment, with maximal mRNA accumulation occurring 1 day after injury and expression persisting to 18 days postaxotomy, a period preceding and coincident with macrophage infiltration. In contrast, by 3 days postaxotomy KC expression is markedly diminished, consistent with the limited neutrophilic response to nerve injury. JE expression was also examined in C57BL/Wld(s) mice, which have delayed Wallerian degeneration associated with a failure of macrophage recruitment, and their parental C57BL/6J strain. Although JE mRNA is inducible in sciatic nerve from C57BL/6J mice, these transcripts are undetectable in injured nerve from C57BL/Wld(s) mice. Our findings suggest that activation of the JE locus is at least partially responsible for macrophage invasion of injured peripheral nerve. Furthermore, defective postaxotomy macrophage recruitment in C57BL/Wld(s) mice may involve a failure of JE induction.