FUNCTIONAL-RELATIONSHIP BETWEEN MAST-CELLS AND C-SENSITIVE NERVE-FIBERS EVIDENCED BY HISTAMINE H-3 RECEPTOR MODULATION IN RAT LUNG AND SPLEEN
FUNCTIONAL-RELATIONSHIP BETWEEN MAST-CELLS AND C-SENSITIVE NERVE-FIBERS EVIDENCED BY HISTAMINE H-3 RECEPTOR MODULATION IN RAT LUNG AND SPLEEN
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DOI：
10.1042/cs0870151
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发表时间：
1994-08-01
期刊：
影响因子：
6
通讯作者：
GARBARG, M
中科院分区：
文献类型：
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作者：
DIMITRIADOU, V;ROULEAU, A;GARBARG, M
1.肥大细胞群体在大鼠肺和脾的特点是存在两个特定的蛋白酶标记物，大鼠肥大细胞蛋白酶I和II，使用组织化学和放射免疫分析技术。结果：1.在肺和脾中发现了3个大小、形态和定位不同的肥大细胞群，并根据肥大细胞蛋白酶I（RMCPI（+））、肥大细胞蛋白酶II（RMCPII（+））或两种蛋白酶同时表达（RMCPI/II+）进行鉴定.在对照组和感染巴西日本圆线虫的大鼠中，所有三种肥大细胞类型都位于降钙素基因相关肽免疫反应（CGRP（+））神经纤维的附近，在感染巴西日本圆线虫的大鼠中，发现RMCP II（+）和RMCPI/II+肥大细胞的数量大量增加。成年大鼠肺组织中有RMCPI/II+细胞，脾组织中有更多.肥大细胞与CGRP（+）C-纤维的相互作用通过评价已知作用于各种类型神经末梢（包括C-纤维）的组胺H-3受体配体的作用来评估。H-3受体配体的影响进行了评估，在对照组，线虫感染的大鼠和pneumatallycapsaicinized大鼠。通过测量[H-3]组氨酸合成[H-3]组胺来评价肥大细胞活性。在对照大鼠中，给予H-3受体激动剂（R）-α-甲基组胺和拮抗剂硫代哌丁胺，分别减少和增强肺和脾中[H-3]组胺的合成，表明组胺通过H-3受体对肥大细胞活性进行了紧张性控制。在空肠中没有发现这种效应，尽管RMCPII（+）肥大细胞与含神经肽的纤维紧密贴壁。H-3受体药物的作用在线虫感染大鼠的肺和脾中得以维持，但在辣椒素处理的大鼠中几乎被抑制.它的结论是，肥大细胞的组胺作用于H-3受体的控制涉及含神经肽的神经，大概反映了操作的本地神经元肥大细胞反馈回路控制过程，如“神经源性炎症”。当肥大细胞在炎症条件下增殖时，该环仍然起作用。这些观察结果表明，组胺H-3受体激动剂的使用可能构成一种新的治疗方法，以限制过度的炎症反应所造成的失调，这种反馈回路。
1. Mast cell populations in rat lung and spleen were characterized by the presence of two specific protease markers, rat mast cell protease I and II, using both histochemical and radioimmunoassay techniques. Three mast cell populations with different size, morphology and localization were found in lung and spleen and were identified according to the expression of rat mast cell protease I (RMCPI(+)) or rat mast cell protease II (RMCPII(+)) or of both proteases (RMCPI/II+).2. All three mast cell types were in the vicinity of calcitonin-gene-related-peptide-immunoreactive (CGRP(+)) nerve fibres in controls as well as in rats infected by Nippostronglyus brasiliensis in which a large increase in the number of both RMCPII(+) and RMCPI/II+ mast cells was found. Ablation of the CGRP(+) fibres by neonatal treatment with capsaicin resulted in a marked increase in the number of RMCPII(+) and RMCPI/II+ cells in lung and, even more, in spleen of adult rats.3. The interaction of mast cells with CGRP(+) C-fibres was assessed pharmacologically by evaluation of the effects of histamine H-3-receptor ligands known to act on various types of nerve endings, including those of C-fibres. The effects of H-3-receptor ligands were assessed in controls, nematode-infected rats and neonatally capsaicinized rats. Mast cell activity was evaluated by measurement of [H-3]histamine synthesis from [H-3]histidine. In control rats, administration of the H-3-receptor agonist (R)-alpha-methylhistamine and antagonist thioperamide, decreased and enhanced respectively [H-3]histamine synthesis in lung and spleen, indicating a tonic control of mast cell activity by histamine via H-3-receptors. Such effects were not found in the jejunum, although RMCPII(+) mast cells are in close apposition with neuropeptide-containing fibres. The effects of the H-3-receptor agents were maintained in lung and spleen of nematode-infected rats, but were almost suppressed in capsaicinized rats.4. It is concluded that the control of mast cells by histamine acting at H-3-receptors involves neuropeptide-containing nerves and presumably reflects the operation of a local neuron-mast cell feedback loop controlling processes such as 'neurogenic inflammation'. This loop still functions when mast cells proliferate in an inflammatory condition. These observations suggest that the use of histamine H-3-receptor agonists may constitute a novel therapeutic approach to limit excessive inflammatory responses resulting from dysregulation of this feedback loop.