Lack of neurokinin-1 receptor expression affects tissue mast cell numbers but not their spatial relationship with nerves

Lack of neurokinin-1 receptor expression affects tissue mast cell numbers but not their spatial relationship with nerves
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DOI:
10.1152/ajpregu.00452.2004
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发表时间:
2005-02-01
影响因子:
2.8
通讯作者:
Saban, R
Saban, R
中科院分区:
医学3区
文献类型:
--
作者:
D'Andrea, MR;Saban, MR;Saban, R

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在胃肠道和泌尿生殖道中,肥大细胞和神经之间的空间联系已被描述。然而,影响肥大细胞和神经之间解剖关系的因素还没有完全确定。有研究表明,P物质的高亲和力受体[神经激肽-1(NK(1))]可能调节这种相互作用。因此,我们评估了从野生型和NK(1)受体基因敲除(NK(1)(-/-))小鼠分离的组织中肥大细胞-神经的关系。我们现在报道,在完全缺乏NK(1)受体表达的情况下,在光镜水平上,胃和膀胱组织中肥大细胞的数量显著增加,肥大细胞与神经之间的解剖关系没有改变。接下来,我们确定移植的肥大细胞是否会保持它们的空间分布、数量和与神经元件的接触。为此目的,用野生型或NK(1)(-/-)骨髓重建肥大细胞缺陷Kit(W)/Kit(W-v)小鼠。肥大细胞与神经的接触无明显差异。这些结果表明,NK(1)受体的表达在肥大细胞数量的调节中是重要的,但在肥大细胞与神经的相互作用中并不重要。此外,肥大细胞和神经之间的相互作用不是通过肥大细胞上NK(1)受体的表达来调节的。肥大细胞迁移及其与神经细胞相互作用的分子途径尚需进一步研究,但Kit(W)/Kit(W-v)小鼠与来自不同基因工程小鼠的肥大细胞重建模型是进一步探讨这些机制的有效途径。
A spatial association between mast cells and nerves has been described in both the gastrointestinal and genitourinary tracts. However, the factors that influence the anatomic relationship between mast cells and nerves have not been completely defined. It has been suggested that the high-affinity receptor for substance P [neurokinin-1 (NK(1))] might modulate this interaction. We therefore assessed mast cell-nerve relationships in tissues isolated from wild-type and NK(1) receptor knockout (NK(1)(-/-)) mice. We now report that, in the complete absence of NK(1) receptor expression, there is a significant increase in the number of mast cells without a change in the anatomic relationship between mast cell and nerves in stomach and bladder tissues at the light microscopic level. We next determined whether transplanted mast cells would maintain their spatial distribution, number, and contact with nerve elements. For this purpose, mast cell-deficient Kit(W)/Kit(W-v) mice were reconstituted with wild-type or NK(1)(-/-) bone marrow. No differences in mast cell-nerve contact were observed. These results suggest that NK(1) receptor expression is important in the regulation of the number of mast cells but is not important in the interaction between mast cells and nerves. Furthermore, the interaction between mast cells and nerves is not mediated through NK(1) receptor expression on the mast cell. Further studies are needed to determine the molecular pathway involved in mast cell migration and interaction with nerve elements, but the model of reconstitution of Kit(W)/Kit(W-v) mice with mast cells derived from different genetically engineered mice is a useful approach to further explore these mechanisms.