Dinh Q Thai, Cryer Annette, Dinh Stephen, Trevisani Marcello, Georgiewa Petra, Chung Fan, Geppetti Pierangelo, Heppt Werner, Klapp Burghard F, Fischer Axel
Department of Internal Medicine, Charité School of Medicine, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany.
Neuropeptides. 2005 Oct;39(5):461-6. doi: 10.1016/j.npep.2005.07.003. Epub 2005 Sep 8.
Protease-activated receptor 2 (PAR2) is activated by trypsin and mast cell tryptase to induce widespread inflammation by unknown mechanisms. Trypsin and tryptase were shown to activate sensory neurons to release substance-P and related peptides to mediate neurogenic inflammation. In the present study, the expression of PAR2 and tachykinins were investigated in rat trigeminal neurons that were identified by retrograde labeling with rhodamine dye from the nasal mucosa by using neuronal tracing in combination with immunohistochemistry. We found that large subpopulation of all trigeminal neurons (43.5+/-2.6%) identified by the pan-neuronal marker PGP 9.5 were stained with PAR2-immunoreactivity. Of all trigeminal neurons, 7.5+/-2.1% were immunoreactive for tachykinins and PAR2, and only 3.9+/-1.7% of all trigeminal neurons expressed tachykinins, but not PAR2-immunoreactivity. The present study also found that a large number trigeminal neurons innervating the nasal mucosa expressed PAR2-immunoreactivity. Of the rhodamine-labeled trigeminal neurons, 52.5+/-1.8% were immunoreactive for only PAR2 expression, 7.3+/-1.9% contained tachykinins and PAR2, and 3.1+/-0.4 of the rhodamine-labeled trigeminal neurons were non-immunoreactive PAR2, but were positive for tachykinins-immunoreactivity. In conclusion, based on the co-localization of PAR2 and tachykinins in trigeminal sensory neurons innervating the nasal mucosa, the present study suggests that, following an activation of PAR2 receptor in tachykinergic neurons by trypsin and mast cell tryptase, there may be a triggering of tachykinin-mediated phenomena such as neurogenic inflammation in allergic or non-allergic rhinitis.
蛋白酶激活受体2(PAR2)可被胰蛋白酶和肥大细胞类胰蛋白酶激活,通过未知机制引发广泛炎症。研究表明,胰蛋白酶和类胰蛋白酶可激活感觉神经元,促使其释放P物质及相关肽类,从而介导神经源性炎症。在本研究中,运用神经元示踪结合免疫组织化学方法,通过用若丹明染料对大鼠鼻黏膜进行逆行标记来鉴定三叉神经元,进而研究PAR2和速激肽在其中的表达情况。我们发现,所有经泛神经元标志物PGP 9.5鉴定的三叉神经元中,有很大一部分亚群(43.5±2.6%)被PAR2免疫反应性染色。在所有三叉神经元中,7.5±2.1%对速激肽和PAR2呈免疫反应性,而所有三叉神经元中仅有3.9±1.7%表达速激肽,但不具有PAR2免疫反应性。本研究还发现,大量支配鼻黏膜的三叉神经元表达PAR2免疫反应性。在经若丹明标记的三叉神经元中,52.5±1.8%仅对PAR2表达呈免疫反应性,7.3±1.9%同时含有速激肽和PAR2,而3.1±0.4%的经若丹明标记的三叉神经元对PAR2无免疫反应性,但对速激肽免疫反应性呈阳性。总之,基于PAR2和速激肽在支配鼻黏膜的三叉感觉神经元中的共定位,本研究表明,在胰蛋白酶和肥大细胞类胰蛋白酶激活速激肽能神经元中的PAR2受体后,可能会引发速激肽介导的现象,如变应性或非变应性鼻炎中的神经源性炎症。