Cloutier Michelle M, Guernsey Linda, Wu Carol A, Thrall Roger S
Department of Pediatrics, University of Connecticut Health Center, Farmington, Connecticut, USA.
Am J Pathol. 2004 May;164(5):1849-56. doi: 10.1016/S0002-9440(10)63743-1.
The electrophysiological properties of cultured tracheal cells (CTCs) were examined in a murine (C57BL/6J), ovalbumin (OVA)-induced model of allergic airway disease (AAD) at early (3-day OVA-aerosol) and peak (10-day OVA-aerosol) periods of inflammation. Transepithelial potential difference, short-circuit current (Isc), and resistance (RT) were lower in CTCs from 10-day OVA-aerosol animals compared to CTCs from naïve mice. In cells cultured for 5 weeks, RT was greater in naive CTCs than in 10-day OVA-aerosol CTCs at all times (P < 0.01). The Isc response to mucosal amiloride (10(-4) mol/L) was increased in CTCs from 10-day OVA-aerosol mice compared to naïve mice (6.0 +/- 0.37 microA/cm2 versus 1.8 +/- 0.56 microA/cm2; P < 0.001) with intermediate values for CTCs from 3-day OVA-aerosol mice. The cAMP-induced increase in Isc was blunted in 10-day OVA-aerosol animals compared to CTCs from naïve mice (9 +/- 12% versus 39 +/- 7%; P < 0.01) with intermediate values for CTCs from 3-day OVA-aerosol mice. There was no difference in mannitol flux in naïve compared to 10-day OVA-aerosol CTCs. Similar results were found using intact tracheas mounted in a perfusion chamber. These data demonstrate changes in airway epithelial cell function in the OVA-induced model of AAD that may contribute to the pathogenesis of airway inflammation.
在小鼠(C57BL/6J)卵清蛋白(OVA)诱导的过敏性气道疾病(AAD)模型中,在炎症早期(OVA雾化3天)和高峰期(OVA雾化10天)检测培养的气管细胞(CTC)的电生理特性。与未接触OVA的小鼠的CTC相比,来自接受OVA雾化10天的动物的CTC的跨上皮电位差、短路电流(Isc)和电阻(RT)较低。在培养5周的细胞中,未接触OVA的CTC的RT在所有时间都高于接受OVA雾化10天的CTC(P<0.01)。与未接触OVA的小鼠相比,来自接受OVA雾化10天的小鼠的CTC对黏膜阿米洛利(10⁻⁴ mol/L)的Isc反应增加(6.0±0.37 μA/cm² 对1.8±0.56 μA/cm²;P<0.001),来自接受OVA雾化3天的小鼠的CTC的Isc反应值介于两者之间。与未接触OVA的小鼠的CTC相比,在接受OVA雾化10天的动物中,cAMP诱导的Isc增加减弱(9±12% 对39±7%;P<0.01),来自接受OVA雾化3天的小鼠的CTC的Isc反应值介于两者之间。未接触OVA的CTC与接受OVA雾化10天的CTC的甘露醇通量没有差异。使用安装在灌注室中的完整气管也得到了类似的结果。这些数据表明,在OVA诱导的AAD模型中气道上皮细胞功能发生了变化,这可能有助于气道炎症的发病机制。