Macrophage infiltration and death in the nerve during the early phases of experimental diabetic neuropathy:: a process concomitant with endoneurial induction of IL-β and p75NTR

Macrophage infiltration and death in the nerve during the early phases of experimental diabetic neuropathy:: a process concomitant with endoneurial induction of IL-β and p75NTR
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DOI:
10.1016/s0022-510x(01)00684-0
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发表时间:
2002-03-15
影响因子:
4.4
通讯作者:
Scarlato, G
Scarlato, G
中科院分区:
医学3区
文献类型:
--
作者:
Conti, G;Scarpini, E;Scarlato, G

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本研究描述了腹腔注射链脲佐菌素(STZ)诱导刘易斯大鼠实验性糖尿病神经病变早期坐骨神经中单核/巨噬细胞的浸润和死亡以及伴随的促炎细胞因子白细胞介素-1 β(IL-1 β)和神经营养因子受体p75(p75 NTR)的神经内膜表达。免疫细胞化学和单网状纤维免疫染色显示,在STZ给药后2周和3周,糖尿病神经中存在巨噬细胞,这些细胞中有15%为TUNEL阳性。IL-1 β在散在的巨噬细胞中明显,并且在沿着少数分离的神经纤维,直到第5周,当它变得不可检测时,伴随着巨噬细胞的完全神经内膜清除。p75 NTR在糖尿病大鼠的坐骨神经中显示出上调,其在STZ给药后第3周开始,在第5周达到峰值,然后在第6周恢复到几乎检测不到的水平。这些结果似乎表明,巨噬细胞和IL-1 β可能参与糖尿病神经病变的发病机制,不仅参与神经损伤,而且还通过p75 NTR诱导促进再生的尝试。(C)2002 Elsevier Science B. V.保留所有权利。
This study describes the infiltration and death of monocyte/macrophages and concomitant endoneurial expression of the pro-inflammatory cytokine interleukin-lbeta (IL-1beta) and neurotrophin receptor p75 (p75NTR) in the sciatic nerve at the early phases of experimental diabetic neuropathy induced in Lewis rats by streptozotocin (STZ) intraperitoneal injection. Immunocytochemistry and single net e fiber immunostaining showed the presence of macrophages in diabetic nerves by weeks 2 and 3 after STZ administration, and the 15% of these cells were TUNEL positive. IL-1beta was evident in scattered macrophages, and along few isolated nerve fibers until week 5, when it became undetectable, in concomitance with complete endoneurial clearance of macrophages. p75NTR showed an up-regulation in the sciatic nerve of diabetic rats that began by week 3 after STZ administration, reached its peak by week 5, and returned then to a barely detectable level by week 6. These findings seem to indicate that macrophages and IL-1beta may be involved in the pathogenesis of diabetic neuropathy, participating not only to nerve damage but also to the promotion of an attempt of regeneration via p75NTR induction. (C) 2002 Elsevier Science B.V. All rights reserved.