MUC5AC mucin release from human airways in vitro: Effects of indomethacin and Bay X1005

BACKGROUND: Increased secretion of mucus is a hallmark of many respiratory diseases and contributes significantly to the airflow limitation experience d by many patients. While the current pharmacological approach to reducing mucus and sputum production in patients is limited, clinical studies have s uggested that drugs which inhibit the cyclooxygenase and/or 5-lipoxygenase enzymatic pathways may reduce secretory activity in patients with airway di sease. Aim: This study was performed to investigate the effects of indomethacin (c yclooxygenase inhibitor) and Bay x1005 (5-lipoxygenase inhibitor) on MUC5AC release from human airways in vitro. Methods: An immunoradiometric assay was used to determine the quantities of MUC5AC present in the biological fluids derived from human airways in vitr o. The measurements were made with a mixture of eight monoclonal antibodies (MAbs; PM8) of which the 21 M1 MAb recognized a recombinant M1 mucin parti ally encoded by the MUC5AC gene. Results: The quantities of MUC5AC detected in the biological fluids derived from human bronchial preparations were not modified after treatment with i ndomethacin (cyclooxygenase inhibitor) and/or an inhibitor of the 5-lipoxyg enase metabolic pathway (BAY x1005). Conclusion: These results suggest that the cyclooxygenase and 5-lipoxygenas e metabolic pathways play little or no role in the release of MUC5AC from h uman airways.