Changes in the density and distribution of sympathetic nerves in spleens from lewis rats with adjuvant-induced arthritis suggest that an injury and sprouting response occurs
Changes in the density and distribution of sympathetic nerves in spleens from lewis rats with adjuvant-induced arthritis suggest that an injury and sprouting response occurs
复制标题
DOI：
10.1002/cne.20640
复制
发表时间：
2005-08-22
影响因子：
2.5
通讯作者：
Bellinger, DL
中科院分区：
文献类型：
--
作者：
Lorton, D;Lubahn, C;Bellinger, DL
先前，我们证明了Lewis大鼠的脾脏中去甲肾上腺素浓度降低，这些大鼠患有佐剂诱导的关节炎（AA），这是一种类风湿关节炎动物模型。本研究扩展了这些发现，研究了疾病发展过程中脾脏交感神经的解剖定位和密度。采用儿茶酚胺的荧光组织化学、酪氨酸羟化酶的形态计量学分析和免疫细胞化学方法，观察Lewis大鼠在诱导关节炎或佐剂治疗后28天脾脏去甲肾上腺素能（NA）神经的分布。在AA大鼠中，NA神经进入脾脏的肝门区交感神经密度比给药大鼠增加了两倍。相反，与非关节炎大鼠相比，关节炎大鼠脾远端NA神经密度明显下降了两倍。两组NA神经均分布于中央小动脉、白髓区、小梁和被膜。与非AA大鼠相比，AA大鼠白髓内NA神经密度降低，红髓内NA神经密度增加。这些发现表明，随着疾病的发展，NA神经在远端区域死亡，并在门部进行代偿性发芽反应，这是一种损伤/发芽反应。NA神经从白髓向红髓的重新分布表明，这些神经信号激活了位于AA红髓的免疫细胞。虽然NA神经重新分布到红髓的机制尚不清楚，但这可能是由于为这些神经提供营养支持的目标免疫细胞从白髓迁移到红髓。NA神经重新分布到红髓中可能在调节免疫功能中起关键作用，从而导致关节炎的慢性炎症阶段。(C) 2005 Wiley-Liss, Inc。
Previously we demonstrated reduced norepinephrine concentrations in spleens from Lewis rats with adjuvant-induced arthritis (AA), an animal model of rheumatoid arthritis. This study extends these findings, examining the anatomical localization and density of sympathetic nerves in the spleen with disease development. Noradrenergic (NA) innervation in spleens of Lewis rats was examined 28 days following adjuvant treatment to induce arthritis or vehicle for the adjuvant by using fluorescence histochemistry for catecholamines, with morphometric analysis and inummocytochemistry for tyrosine hydroxylase. In AA rats, sympathetic nerve density in the hilar regions, where NA nerves enter the spleen, was increased twofold over that observed in vehicle-treated rats. In contrast, there was a striking twofold decline in the density of NA nerves in splenic regions distal to the hilus in arthritic rats compared with nonarthritic rats. In both treatment groups, NA nerves distributed to central arterioles, white pulp regions, trabeculae, and capsule. However, NA nerve density was reduced in the white pulp but was increased in the red pulp in AA rats compared with non-AA rats. These findings indicate an injury/sprouting response with disease development whereby NA nerves die back in distal regions and undergo a compensatory sprouting response in the hilus. The redistribution of NA nerves from white pulp to red pulp suggests that these nerves signal activated immune cells localized in the red pulp in AA. Although the mechanisms of this redistribution of NA nerves into the red pulp are not known, it may be due to migration from white pulp to red pulp of target immune cells that provide trophic support for these nerves. The redistribution of NA nerves into the red pulp may be critical in modulating immune functions that contribute to the chronic inflammatory stages of arthritis. (C) 2005 Wiley-Liss, Inc.