Pneumologie 2015; 69 - A6
DOI: 10.1055/s-0035-1556598

Regional differences in Cl- conductance in human nasal epithelial primary cells (hNEpC) of patients with chronic rhinosinusitis

T Albrecht 1, 2, J Salomon 1, H Stichnoth 1, I Baumann 2, MA Mall 1
  • 1Department of Translational Pulmonology, Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg
  • 2Department of Otorhinolaryngology, Head and Neck Surgery, Medical Center of the University of Heidelberg

Chronic rhinosinusitis (CRS) is considered as a common disease with symptoms such as nasal obstruction and discharge. CRS also is a prevalent feature of cystic fibrosis and other lung diseases (e.g. primary ciliary dyskinesia). The underlying pathophysiologic mechanisms of CRS have not yet been clearly identified. The purpose of this study is to functionally characterise epithelial chloride conductance in two distinct nasal regions in patients with CRS.

hNEpC were freshly isolated from nasal tissue close to processus uncinatus (hNEpC-PU) and paranasal sinus (ethmoid bone, hNEpC-PS) from patients undergoing polyps resection. Transepithelial chloride currents were measured in Ussing chambers. mRNA expression profiles of predominant chloride channels such as CFTR, TMEM16A and SLC26A9 as well as subunits of the sodium channel ENaC (α, β and γ) were determined using qPCR.

Basal short-circuit current (Isc) of hNEpC-PU was higher (47.0 ± 2.3µA/cm2) compared to hNEpC-PS (19.6 ± 2.0µA/cm2). The effect of amiloride was also increased in hNEpC-PU (ΔIsc = 3.8 ± 0.6µA/cm2) when compared to hNEpC-PS (ΔIsc = 2.7 ± 0.4µA/cm2). IBMX/Forskolin stimulated Cl- secretion in hNEpC-PU (ΔIsc = 2.1 ± 0.6µA/cm2) and in hNEpC-PS (ΔIsc = 2.4 ± 0.7µA/cm2). Subsequent treatment with UTP resulted in values of ΔIsc = 1.0 ± 0.4µA/cm2 (hNEpC-PU) and lower stimulative effects in hNEpC-PS (ΔIsc = 0.5 ± 0.1µA/cm2), respectively. In both tissues, CFTRinh-172 efficiently blocked Cl- secretion (hNEpC-PU: ΔIsc = 2.9 ± 0.6µA/cm2 and hNEpC-PS: ΔIsc = 3.8 ± 0.5µA/cm2, respectively). On mRNA level αENaC was expressed highest, followed by βENaC and γENaC. TMEM16A and SLC26A9 were measured at similar levels, whereas CFTR was approx. 20-fold lower expressed. No statistical differences between hNEpC-PU and hNEpC-PS were obtained.

We observed differences in ion transport properties along the human nasal epithelial barrier with no differences in the expression pattern. Ussing chamber measurements using hNEpC of CRS patients provide a promising tool to further evaluate the underlying pathophysiologic mechanisms and to elucidate involved chloride channels.

*Presenting author