Functional relationships between sensory nerve fibers and mast cells of dura mater in normal and inflammatory conditions
Functional relationships between sensory nerve fibers and mast cells of dura mater in normal and inflammatory conditions
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DOI：
10.1016/s0306-4522(96)00488-5
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发表时间：
1997-04-01
期刊：
影响因子：
3.3
通讯作者：
Garbarg, M
中科院分区：
文献类型：
--
作者：
Dimitriadou, V;Rouleau, A;Garbarg, M
在这项研究中，我们的特点是肥大细胞在大鼠硬脑膜的表型和它们的拓扑结构和功能与C-纤维在正常和炎症条件下的关系。三个肥大细胞群体具有不同的大小，形态和定位的特点，其内容的特定中性丝氨酸蛋白酶。它们表现出与大鼠肥大细胞蛋白酶I、大鼠肥大细胞蛋白酶II或两种蛋白酶相对应的免疫反应性。使用共聚焦显微镜，观察到所有三种肥大细胞类型的密切贴壁（距离小于100 nm）降钙素基因相关肽和P物质免疫反应性神经纤维在控制和大鼠感染的线虫Nippostrongylus巴西。在线虫感染或新生儿辣椒素治疗后，在硬脑膜节段内发现大鼠肥大细胞蛋白酶II免疫反应性肥大细胞的数量大量增加（分别为+1478%和+596%），而没有伴随的大鼠肥大细胞蛋白酶I或大鼠肥大细胞蛋白酶I/II免疫反应性肥大细胞的变化。在这两种条件下，肥大细胞数量的增加伴随着组织提取物中大鼠肥大细胞蛋白酶II水平的显著增加（线虫感染后+281%，辣椒素处理后+36%）。肥大细胞与硬脑膜中感觉神经纤维的功能相互作用通过评价施用L-[H-3]组氨酸后[H-3]组胺的合成来评估，这是肥大细胞活性的指标。H-3受体激动剂（R）-α-甲基组胺（15 mg/kg，i. p.）没有效果，但给予II受体拮抗剂硫代哌丁胺（10 mg/kg，i. p.），导致[H-3]组胺合成显著增加（+62%）。这种作用在新生辣椒素处理的大鼠中减少，但没有完全抑制（+35%），很可能是因为部分去神经支配，如通过监测降钙素基因相关肽免疫反应性所评估的。感觉神经纤维和肥大细胞积极合成和释放组胺，形成一个短的抑制性反馈回路，涉及连接前的H-3-受体，可以调节促炎介质的释放，从而限制炎症反应的程度。(C)1997年IBRO。
In this study, we have characterized the phenotype of mast cells in rat dura mater and their topological and functional relationships with C-fibers in normal and inflammatory conditions. Three mast cell populations with different size, morphology and localization were characterized by their content of specific neutral serine proteases. They showed immunoreactivity corresponding to rat mast cell protease I, rat mast cell protease II, or both proteases. Using confocal microscopy, all three mast cell types were observed in close apposition (distance less than 100 nm) to calcitonin gene-related peptide- and substance P-immunoreactive nerve fibers in both controls and rats infected with the nematode Nippostrongylus brasiliensis. After nematode infection or neonatal treatment with capsaicin, a large increase in the number of rat mast cell protease II-immunoreactive mast cells was found within dura mater segments (+1478% and +596%, respectively), without concomitant changes of rat mast cell protease I- or rat mast cell protease I/II-immunoreactive mast cells. Under both these conditions, the increase in mast cell number was accompanied by a significant increase in rat mast cell protease II level within tissue extracts (+281% after nematode infection and +36% after capsaicin treatment). The functional interaction of mast cells with sensory nerve fibers in the dura mater was assessed by evaluating [H-3]histamine synthesis after administration of L-[H-3]histidine, an index of mast cell activity. The H-3 receptor agonist (R)-alpha-methylhistamine (15 mg/kg, i.p.) had no effect, but administration of the II, receptor antagonist, thioperamide (10 mg/kg, i.p.), resulted in a significant increase of [H-3]histamine synthesis (+62%). This effect was reduced in neonatal capsaicin-treated rats, but not completely suppressed (+35%), very likely because of partial denervation, as assessed by monitoring calcitonin gene-related peptide immunoreactivity.It is concluded that, in the dura mater, as in peripheral tissues, sensory nerve fibers and mast cells actively synthesizing and releasing histamine form a short inhibitory feedback loop involving prejunctional H-3-receptors that could regulate the release of pro-inflammatory mediators, thus limiting the extent of inflammatory reactions. (C) 1997 IBRO.