TNFα modifies ciliary beat frequency in response to viscous overload, associated to changes in intracellular calcium in human respiratory ciliated cells

Abstract

Introduction: Pathologic sinonasal secretions and elevated levels of tumor necrosis factor alpha (TNFa) have been noted in sinus mucosa of patients with chronic sinusitis. Respiratory ciliated cells have a functional reserve that allows them to autoregulate their ciliary beat in response to the changes in viscosity, modifying intracellular calcium levels [Ca⁺²]_ic. Aim: Our goal was to determínate if TNFa affect this autoregulation to viscosity and calcium homeostasis. Material and Method: Primary cultures from adenoid tissue explants. Ciliary beat frequency (CBF) was recorded using microphotodensitometry. Cultures were treated with TNFa (10 ng/ml) or control during 24 and 48 hours. Viscosity was increased by adding dextran 500 10% and 20%. [Ca⁺²]_ic was determined in cells loaded with fura- 2AM. Results: 48 hours treatment with TNFa produced a significant decrease in CBF at low viscosity, significant increase in [Ca⁺²]_ic and greater decrese in CBF in cultures treated with thapsigargin (endoplasmic calcium-ATPase pump blocker). Conclusions: After 48 hours of exposure to TNFa a negative effect in the adaptation mechanism to a low viscous media is observed in ciliated cells, probably secondary to changes in homeostasis of [Ca⁺²]_ic.