Proton secretion in freshly excised sinonasal mucosa from asthma and sinusitis patients.

Proton secretion in freshly excised sinonasal mucosa from asthma and sinusitis patients.
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DOI:
10.2500/ajra.2009.23.3389
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发表时间:
2009-11
影响因子:
2.6
通讯作者:
Fischer H
Fischer H
中科院分区:
医学3区
文献类型:
--
作者:
Cho DY;Hajighasemi M;Hwang PH;Illek B;Fischer H

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气道的一个主要功能是从吸入的空气中清除病原体,从而防止感染。呼吸道上皮细胞分泌质子是先天性宿主防御机制的组成部分,涉及质子通道(氢电压门控通道1,HVCN 1)。本研究的目的是通过使用新鲜切除的人鼻窦组织来测量慢性鼻窦炎的哮喘和非哮喘患者的气道炎症对酸分泌的影响。在鼻窦手术期间,从具有三种不同状况(正常、慢性鼻窦炎(CRS)、CRS伴哮喘)的受试者中采集鼻或鼻窦粘膜。在Ussing型腔室中使用pH恒定滴定技术测量每个组织的质子(H+)分泌速率。使用ZnCl2作为阻断剂鉴定HVCN 1质子通道对酸分泌的贡献。从诊断为慢性鼻窦炎(CRS)和哮喘的受试者中分离的鼻上皮具有粘膜平衡pH = 6.95(n = 5),其显著低于在来自正常(n = 5,7.35 ± 0.21)或来自没有哮喘的CRS受试者(n = 5,7.33 ± 0.15)的鼻上皮中发现的平衡pH。当碱化粘膜pH至8.0时,CRS哮喘患者(n = 5)的鼻上皮细胞以135.1 ± 46.2 nmol·min-1·cm-2的速率分泌H+。与正常(73.3 ± 39.3 nmol·min-1·cm-2,n = 8)或无哮喘的CRS(51.4 ± 27.7 nmol·min-1·cm-2,n = 7)相比,该速率显着较高。ZnCl_2对H~+分泌的抑制作用在正常人中为70%,在无哮喘的CRS中为52.6%,在有哮喘的CRS中为50.8%。新鲜切除的人鼻和鼻窦上皮细胞分泌酸穿过顶端细胞膜。从哮喘CRS患者中分离的鼻窦组织显示出较低的粘膜pH值和较高的H+分泌速率,并且在所有组中约50 - 70%的酸分泌是由HVCN 1 H+通道介导的。酸分泌过多可能是CRS哮喘患者上皮损伤的原因之一。
One major function of the airways is to inactivate and remove pathogens from inhaled air and thereby prevent infection. The secretion of protons by the airway epithelium presents an integral part of the innate host defense mechanism and involves the proton channel (hydrogen voltage-gated channel 1, HVCN1). The purpose of this study was to measure the effect of airway inflammation on acid secretion in asthmatic and non-asthmatic patients with chronic rhinosinusitis by using freshly excised human sinonasal tissue. Nasal or sinus mucosa from subjects with three different conditions (normal, chronic rhinosinusitis (CRS), CRS with asthma) was harvested during sinus surgery. The rate of proton (H+) secretion by each tissue was measured using the pH-stat titration technique in an Ussing type chamber. The contribution of the HVCN1 proton channel to acid secretion was identified using ZnCl2 as a blocker. Nasal epithelia isolated from subjects with a diagnosis of both chronic rhinosinusitis (CRS) and asthma had a mucosal equilibrium pH = 6.95 (n = 5), which was significantly lower than the equilibrium pH found in nasal epithelia from normal (n = 5, 7.35 ± 0.21) or from subjects with CRS without asthma (n = 5, 7.33 ± 0.15). When alkalinizing the mucosal pH to 8.0, nasal epithelia from CRS with asthma (n = 5) secreted H+ at a rate of 135.1±46.2 nmol·min−1·cm−2. This rate was significantly higher compared to normal (73.3±39.3 nmol·min−1·cm−2, n = 8) or CRS without asthma (51.4±27.7 nmol·min−1·cm−2, n = 7). Mucosal addition of ZnCl2 blocked H+ secretion by 70% in normal, 52.6% in CRS without asthma, and by 50.8% in CRS with asthma. Freshly excised human nasal and sinus epithelia secrete acid across the apical cell membrane. Sinonasal tissue isolated from asthmatic CRS patients showed lower mucosal pH values and higher rates of H+ secretion than CRS and normal subjects, and ~50–70% of acid secretion was mediated by the HVCN1 H+ channel in all groups. Excessive acid secretion might contribute to epithelial injury in CRS patients with asthma.
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发表时间: 2004-09-01
期刊: LUNG
影响因子: 5
作者:
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