Potential Role of Abnormal Ion Transport in the Pathogenesis of Chronic Sinusitis

Abstract

To create well-differentiated cultures of normal and chronic sinusitis paranasal sinus epithelial cells and to compare their electrophysiologic properties. Design: In vitro investigation using primary sinus epithelial cells, initially cultured on plastic tissue culture dishes. Cells were characterized by means of immunocytochemical analysis and then passaged to air-liquid interface culture conditions. The morphologic features of air-liquid interface cultures were assessed using light and electron microscopy. Epithelial Na ϩ channel, Na ϩ-K ϩ-2Cl − cotransporter, cystic fibrosis transmembrane conductance regulator, and Ca 2ϩ-activated Cl − channel function were investigated in Ussing chambers. Subjects: Specimens were obtained from 15 patients undergoing transsphenoidal pituitary procedures, tumor removal, or trauma repair and from 9 patients with chronic sinusitis. Results: After culture at an air-liquid interface for 21 days, the epithelium was pseudostratified and contained basal, mucous secretory, and ciliated cells. There were no detectable morphologic differences between normal and chronic sinusitis cells. In cultures of normal cells, median basal short circuit current was 4.7 µA/cm 2 , and Na ϩ transport, defined as the amiloride hydrochloridesensitive component, was approximately 20% of the total. Basal and amiloride-sensitive short circuit currents were greater in cultures of chronic sinusitis cells. Basal short circuit currents in both types of cultures were insensitive to the Cl − transport inhibitor bumetanide, but all responded to forskolin or uridine triphosphate. After amiloride pretreatment, forskolin and uridine triphosphate responses were greater in chronic sinusitis cells. Conclusions: We established methods for welldifferentiated sinus epithelial cultures. The cells exhibited Na ϩ absorption and Cl − secretion, and elevated rates of ion transport may be pathophysiologically relevant in chronic sinusitis.

Comparison of Vectorial Ion Transport in Primary Murine Airway and human Sinonasal Air-Liquid Interface Cultures, Models for Studies of Cystic Fibrosis, and other Airway Diseases

“…14 The discrepancy could result from dissimilar culture methods, use of nasal polyp cells versus differentiated and otherwise intact sinus tissue in the present experiments, or local variations in ion transport proper- ties within the nose. However, our results are consistent with those of Dejima et al 15 and their findings in normal cultured paranasal sinus epithelium.…”

Differential Chloride Secretory Capacity in Transepithelial Ion Transport Properties in Chronic Rhinosinusitis

“…30 Dejima et al demonstrated that cells from CRS exhibited relatively large I sc responses to amiloride, suggesting increased Na þ transport rates. 3 However, in the current study, there was no statistical difference between controls and CRS. Wang et al's in vivo nasal potential difference (PD) measurement also showed a mean DPD (changes in PD) that was similar to that of controls after exposure to amiloride.…”

Increased expression of the epithelial anion transporter pendrin/SLC26A4 in nasal polyps of patients with chronic rhinosinusitis

“…This weak association may be due to small sample size, variability of human samples, variability introduced due to sample isolation and processing and importantly, suggests alternate modes of regulation and function. Since pendrin is also involved in regulating ion transport in airway epithelial cells, we speculate that elevated pendrin in nasal polyps may lead to dysregulated ion transport activity (increased Cl − absorption) as proposed by others 11, 12 .…”