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Sensory neuropeptides are potent chemoattractants for human basophils in vitro.

机译:感觉神经肽是人类嗜碱性粒细胞在体外的有效趋化剂。

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摘要

The sensory neuropeptides secretoneurin (SN) and substance P (SP) are involved in neurogenic rhinitis. A possible interaction with basophils has not been reported to date. Basophils were isolated from healthy donors by magnetic cell sorting technique and migration was explored using Boyden microchemotaxis chambers. SN [10(-8)M] and SP [10(-6) to 10(-8)M] proved to be chemoattractants equally potent to FMLP [10(-8)M] or LPS [10 pg/ml]. Specific anti-SN antibodies and a trypsinization preparation of SN were used to determine the specificity of the SN effect on basophils. The preincubation of basophils with neurokinin-1 (NK-1) or -2 (NK-2) receptor antagonists revealed the SP effect to act via NK-1 receptors in basophils. In addition, we were able to show phosphodiesterases and phosphoinositide-3 kinases to be engaged in the downstream signalling pathway. Our observations reveal for the first time a link between basophils, which are engaged in allergic processes, and the neuropeptides SN and SP. Furthermore, our data might suggest phosphodiesterases or phosphoinositide-3 kinases to be new therapeutic targets for the treatment of allergic diseases such as asthma or allergic rhinitis.
机译:感觉神经肽促分泌素(SN)和P物质(SP)参与神经源性鼻炎。迄今为止尚未报道与嗜碱性粒细胞的可能相互作用。通过磁性细胞分选技术从健康供体中分离出嗜碱性粒细胞,并使用Boyden微趋化室探索迁移。 SN [10(-8)M]和SP [10(-6)到10(-8)M]被证明是对FMLP [10(-8)M]或LPS [10 pg / ml]具有同等效力的趋化剂。使用特定的抗SN抗体和SN的胰蛋白酶处理制剂来确定SN对嗜碱粒细胞的特异性。嗜碱性粒细胞与神经激肽-1(NK-1)或-2(NK-2)受体拮抗剂的预温育揭示了SP效应通过嗜碱性粒细胞中的NK-1受体起作用。此外,我们能够显示磷酸二酯酶和磷酸肌醇3激酶参与下游信号通路。我们的观察首次揭示了参与变态反应的嗜碱性粒细胞与SN和SP神经肽之间的联系。此外,我们的数据可能表明磷酸二酯酶或磷酸肌醇3激酶是治疗过敏性疾病(如哮喘或过敏性鼻炎)的新治疗靶标。

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