Abdellah Nada, van Remoortel Samuel, Mohey-Elsaeed Omnia, Mustafa Mohamed-Nabil, Ahmed Yasser A, Timmermans Jean-Pierre, Buckinx Roeland
Histology Department, Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt.
Laboratory of Cell Biology & Histology, University of Antwerp, Antwerp, Belgium.
Anat Rec (Hoboken). 2018 Jun;301(6):1103-1114. doi: 10.1002/ar.23780. Epub 2018 Feb 7.
Neuropeptides AF (NPAF), FF (NPFF) and SF (NPSF) are RFamide neuropeptides known to be widely expressed in the mammalian central nervous system, where they fulfill a wide range of functions with pain modulation being the most prominent one. Recent evidence indicates that RFamides act as mediators in mast cell-sensory nerve communications related to allergic disease. Previous work by our group has shown that the expression levels of some members of the Mas-related gene receptor (Mrgpr) family in both enteric neurons and mucosal mast cells change during intestinal inflammation. The Mrgpr subtypes C11 and A4 can be activated by NPAF, while A1 and C11 are triggered by NPFF. The aim of the present study was to investigate whether RFamides of the NPFF group are expressed in the gastrointestinal tract and to identify possible targets and receptors that might be involved in RFamide-associated mast cell modulation. To this end, the expression and distribution patterns of NPFF/AF receptors and the NPFF precursor protein were determined in bone marrow-derived mucosal mast cells (BMMCs) by immunocytochemistry and (RT-) PCR. BMMCs were found to express MrgprA4 and A1, and functional analysis of the effects of NPAF by means of a β-hexosaminidase assay, mMCP-1 ELISA, electron microscopy and live cell calcium imaging revealed a piecemeal degranulation induced by NPAF. However, knock-out of MrgprA4 and A1 did not reduce the effect of NPAF, indicating that the BMMC response to NPAF was receptor independent. ProNPFF was expressed in neurons and BMMCs, suggesting that both cell types are potential sources of NPAF in situ. Our results show that the RFamide NPAF can be considered as a novel modulator of BMMC activity in the neuro-immune communication in the gastrointestinal tract, although the exact signaling pathway remains to be elucidated. Anat Rec, 00:000-000, 2018. © 2018 Wiley Periodicals, Inc. Anat Rec, 301:1103-1114, 2018. © 2018 Wiley Periodicals, Inc.
神经肽AF（NPAF）、FF（NPFF）和SF（NPSF）是已知在哺乳动物中枢神经系统中广泛表达的RFamide神经肽，它们在其中发挥多种功能，其中疼痛调节最为突出。最近的证据表明，RFamides在与过敏性疾病相关的肥大细胞 - 感觉神经通讯中充当介质。我们小组之前的工作表明，在肠道炎症期间，肠道神经元和黏膜肥大细胞中Mas相关基因受体（Mrgpr）家族某些成员的表达水平会发生变化。Mrgpr亚型C11和A4可被NPAF激活，而A1和C11则由NPFF触发。本研究的目的是调查NPFF组的RFamides是否在胃肠道中表达，并确定可能参与RFamide相关肥大细胞调节的潜在靶点和受体。为此，通过免疫细胞化学和（RT - ）PCR在骨髓来源的黏膜肥大细胞（BMMCs）中测定NPFF/AF受体和NPFF前体蛋白的表达及分布模式。发现BMMCs表达MrgprA4和A1，并且通过β - 己糖胺酶测定、mMCP - 1 ELISA、电子显微镜和活细胞钙成像对NPAF作用的功能分析揭示了NPAF诱导的颗粒逐片释放。然而，敲除MrgprA4和A1并没有降低NPAF的作用，表明BMMC对NPAF的反应不依赖于受体。ProNPFF在神经元和BMMCs中表达，表明这两种细胞类型都是原位NPAF的潜在来源。我们的结果表明，尽管确切的信号通路仍有待阐明，但RFamide NPAF可被视为胃肠道神经免疫通讯中BMMC活性的新型调节剂。《解剖学记录》，00:000 - 000，2018年。©2018威利期刊公司。《解剖学记录》，301:1103 - 1114，2018年。©2018威利期刊公司。
