Furuno Tadahide, Ma Donglai, van der Kleij Hanneke P M, Nakanishi Mamoru, Bienenstock John
Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
Neurosci Lett. 2004 Dec 6;372(3):185-9. doi: 10.1016/j.neulet.2004.08.008.
In virtually all tissues of the body, mast cells are closely associated with nerve fibers, mostly of sensory origin. While mast cells can be activated by substance P, evidence for the involvement of NK-1 receptors is very limited. To study functional interactions between mast cells and peripheral nerves, bone marrow-derived mast cells (BMMC) and superior cervical ganglia (SCG) were co-cultured. Murine bone marrow-derived mast cells are homologues for mucosal mast cells and have recently been shown to express NK-1 receptors. Bi-directional interaction was studied using a fluorescent calcium indicator as an index of cellular activation. Scorpion venom, not affecting BMMC by itself, caused a rapid increase in neurite fluorescence subsequently followed by activation of the mast cell. The latter was inhibited by the NK-1 receptor antagonist SR140333, showing the direct involvement of substance P and its receptor in this co-culture system. Activation of BMMC seemed to be directly correlated with extent of NK-1 receptor expression. Immature c-kit positive cells not expressing NK-1 gave a negligible response to neurite activation. In addition, there was a maximum stimulation occurring when NK-1 expression exceeded 16% on BMMC after cytokine stimulation. Our findings show that the expression of NK-1 receptors appears to be important for nerve-mast cell communication.
在人体几乎所有组织中,肥大细胞都与神经纤维紧密相连,这些神经纤维大多起源于感觉神经。虽然P物质可激活肥大细胞,但关于NK-1受体参与其中的证据非常有限。为了研究肥大细胞与外周神经之间的功能相互作用,将骨髓来源的肥大细胞(BMMC)与颈上神经节(SCG)进行了共培养。小鼠骨髓来源的肥大细胞是黏膜肥大细胞的同源物,最近已证明其表达NK-1受体。使用荧光钙指示剂作为细胞活化指标研究了双向相互作用。蝎毒本身不影响BMMC,但可导致神经突荧光迅速增加,随后肥大细胞被激活。后者被NK-1受体拮抗剂SR140333抑制,表明P物质及其受体直接参与了该共培养系统。BMMC的激活似乎与NK-1受体的表达程度直接相关。不表达NK-1的未成熟c-kit阳性细胞对神经突激活的反应可忽略不计。此外,细胞因子刺激后,当BMMC上NK-1的表达超过16%时,会出现最大刺激。我们的研究结果表明,NK-1受体的表达似乎对神经-肥大细胞通讯很重要。