Abstract
Increased secretion of mucus is a hallmark of many respiratory diseases and contributes significantly to the airflow limitation experienced by many patients. While the current pharmacological approach to reducing mucus and sputum production in patients is limited, clinical studies have suggested that drugs which inhibit the cyclooxygenase and/or 5-lipoxygenase enzymatic pathways may reduce secretory activity in patients with airway disease. This study was performed to investigate the effects of indomethacin (cyclooxygenase inhibitor) and Bay x 1005 (5-lipoxygenase inhibitor) on MUC5AC release from human airways in vitro. An immunoradiometric assay was used to determine the quantities of MUC5AC present in the biological fluids derived from human airways in vitro. The measurements were made with a mixture of eight monoclonal antibodies (MAbs; PM8) of which the 21 M1 MAb recognized a recombinant M1 mucin partially encoded by the MUC5AC gene. The quantities of MUC5AC detected in the biological fluids derived from human bronchial preparations were not modified after treatment with indomethacin (cyclooxygenase inhibitor) and/or an inhibitor of the 5-lipoxygenase metabolic pathway (BAY x 1005). These results suggest that the cyclooxygenase and 5-lipoxygenase metabolic pathways play little or no role in the release of MUC5AC from human airways.
Highlights
An increase in the quantities of the metabolites of the cyclooxygenase and 5-lipoxygenase enzymatic pathways has been demonstrated in sputum derived from asthmatic patients[1,2] and patients with chronic bronchitis.[3,4] In clinical studies,[5] involving patients treated with inhibitors of these enzymatic pathways, a significant reduction in sputum volume has been reported
Initial reports have indicated that exposure of human airway cultured cell explants to indomethacin caused an increase in mucus secretion, when the incorporation of 3H-glucosamine was used as the index of glycoprotein secretory activity.[8]
Steroid inhalation or injection has been reported to significantly reduce sputum production in asthmatic patients[2] and in isolated human airways, steroids significantly reduced glycoprotein secretion.[9]. These data suggest that further studies concerning the effects of inhibition of the cyclooxygenase and/or lipoxygenase pathways on secretory activity may be warranted since there remains considerable controversy concerning such inhibition in the human respiratory tract
Summary
An increase in the quantities of the metabolites of the cyclooxygenase and 5-lipoxygenase enzymatic pathways has been demonstrated in sputum derived from asthmatic patients[1,2] and patients with chronic bronchitis.[3,4] In clinical studies,[5] involving patients treated with inhibitors of these enzymatic pathways, a significant reduction in sputum volume has been reported. These observations suggest that eicosanoids may be involved in airway inflammation and modify the secretory activity in the human respiratory tract. Conclusion: These results suggest that the cyclooxygenase and 5-lipoxygenase metabolic pathways play little or no role in the release of MUC5AC from human airways
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