Morphological and functional demonstration of rat dura mater mast cell-neuron interactions in vitro and in vivo
Morphological and functional demonstration of rat dura mater mast cell-neuron interactions in vitro and in vivo
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DOI：
10.1016/s0006-8993(99)01855-7
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发表时间：
1999-12-04
期刊：
影响因子：
2.9
通讯作者：
Theoharides, TC
中科院分区：
文献类型：
--
作者：
Rozniecki, JJ;Dimitriadou, V;Theoharides, TC
肥大细胞来源于不同的骨髓前体，并在干细胞因子、神经生长因子（NGF）和某些白细胞介素的影响下在组织中成熟。颅内肥大细胞首先出现在脑膜中，位于血管周围靠近神经元。它们可以被三叉神经的逆向刺激激活，也可以被急性制动应激激活。P物质（SP）和促肾上腺皮质激素释放激素（CRH）在刺激肥大细胞释放血管活性、炎症和伤害感受分子方面特别有效。这些发现表明肥大细胞可能参与神经炎症，如偏头痛。在这项研究中，硬脑膜肥大细胞具有结缔组织肥大细胞（CTMC）的特性，因为它们含有组胺，肝素和大鼠肥大细胞蛋白酶I（RMCP-I）。肥大细胞定位接近SP阳性神经元免疫细胞化学和肥大细胞神经元接触也记录使用扫描电子显微镜。SP和卡巴胆碱刺激硬脑膜，可在原位释放组胺。硬膜与雌二醇的预孵育略有增加组胺释放的SP，可能通过雌激素受体介导的影响，确定硬膜肥大细胞。急性应激制动导致硬脑膜肥大细胞脱颗粒，这是防止预处理与CRH中和抗体或CRH受体拮抗剂。本研究结果进一步阐明了颅内肥大细胞的生物学，并支持它们参与偏头痛的病理生理学，偏头痛是由压力引起或恶化的。(C)1999 Elsevier Science B. V.保留所有权利。
Mast cells derive from a distinct bone marrow precursor and mature in tissues under the influence of stem cell factor, nerve growth factor (NGF) and certain interleukins. Intracranial mast cells first appear in the meninges and are located perivascularly close to neurons. They can be activated by antidromic stimulation of the trigeminal nerve, as well as by acute immobilization stress. Substance P (SP) and corticotropin-releasing hormone (CRH) are particularly potent in stimulating mast cell release of vasoactive, inflammatory and nociceptive molecules. These findings have suggested that mast cells may be involved in neuroinflammatory conditions, such as migraines. In this study, dura mast cells were shown to have characteristics of connective tissue mast cells (CTMC) as they contained histamine, heparin and rat mast cell protease I (RMCP-I). Mast cells were localized close to SP-positive neurons immunocytochemically and mast cell-neuron contacts were also documented using scanning electron microscopy. Dura stimulated by SP and carbachol in situ released histamine. Preincubation of dura with estradiol slightly augmented histamine release by SP, an effect possibly mediated through estrogen receptors identified on dura mast cells. Acute stress by immobilization led to dura mast cell degranulation which was prevented by pretreatment with a neutralizing antibody to CRH or a CRH receptor antagonist. The present results further clarify the biology of intracranial mast cells and support their involvement in the pathophysiology of migraines which are precipitated or worsened by stress. (C) 1999 Elsevier Science B.V. All rights reserved.