Pneumologie 2016; 70 - P37
DOI: 10.1055/s-0036-1584641

Nasal epithelia cultures of patients with chronic rhinosinusitis show altered ion transport capacities

JJ Salomon 1, T Albrecht 2, H Scheuermann 1, I Baumann 2, MA Mall 1
  • 1Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, Heidelberg, Germany
  • 2Medical Center of the University of Heidelberg, Heidelberg, Germany

Rationale. Chronic rhinosinusitis (CRS) is a very common chronic disorder of the upper airways and frequently observed in patients with cystic fibrosis (CF). The underlying pathophysiologic mechanisms may result in sinonasal inflammation, deficient mucus clearance or altered nasal epithelial ion transport, however, it is still rather unexploited. The purpose of this study was to functionally characterise the epithelial ion transport in cultured nasal epithelia of patients with CRS.

Methods. Nasal tissues of patients with CRS undergoing polyps resection and turbinate tissue from healthy controls were utilized to freshly isolate nasal epithelial primary cells (hNEpC). HNEpC were cultured under air-interfaced conditions and transepithelial short-circuit currents (Isc) were measured in Ussing chambers in the absence and presence of pretreatment with the type 2 cytokine IL-13.

Results. Bioelectrical studies revealed a significantly reduced basal Isc in hNEpC cell monolayers of patients with CRS compared to controls (CRS Isc = 18.2 ± 1.7µA/cm2 vs. control Isc = 38.1 ± 6.5µA/cm2, p < 0.05). Further, the amiloride-insensitive current reflecting constitutive Cl- secretion was significantly diminished in CRS (15.5 ± 1.7µA/cm2) compared to control cell monolayers (33.8 ± 6.6µA/cm2, p < 0.05). UTP-induced responses reflecting Ca2+-activated Cl- secretion were substantially lower in CRS (0.0 ± 0.2µA/cm2) vs. control (0.7 ± 0.2µA/cm2). Based on previous studies demonstrating activation of the Ca2+-activated Cl- channel TMEM16A by the type 2 cytokine IL-13, we next compared UTP-mediated Isc in CRS and control cultures in the presence of IL-13. UTP-mediated Cl- secretory responses in IL-13 pretreated cultures increased in CRS to 1.9 ± 0.5µA/cm2 (p < 0.01), but only ˜2-fold (1.2 ± 0.4µA/cm2) in control cultures.

Conclusions. We observed substantial differences in the ion transport capacity of nasal epithelial cultures from patients with CRS compared to controls. Our results suggest an abnormal epithelial ion transport partially accountable to TMEM16A and support further investigation of this epithelial dysregulation in the pathogenesis of CRS.