Effect of benzydamine on exocytosis and respiratory burst in human neutrophils and mononuclear phagocytes.
The effect of benzydamine on stimulus-dependent respiratory burst activity and enzyme release was tested in human neutrophils, monocytes and monocyte-derived macrophages. Established anti-inflammatory compounds, indomethacin, phenylbutazone and bufexamac, were tested for comparison. Care was taken to avoid cytotoxic or cytolytic concentrations of the test compounds, and their effect on release of lactate dehydrogenase was also tested. Release of specific and azurophil granules contents were induced in human neutrophils by A23187, PMA and fMLP with and without cytochalasin B pretreatment. Benzydamine inhibited stimulus-dependent release of vitamin B12-binding proteins, a marker for the specific granules, in a concentration-dependent fashion. By contrast, phenylbutazone and bufexamac were practically inactive. The effect of benzydamine on exocytosis of azurophil granules was tested in cytochalasin B-pretreated neutrophils. Benzydamine, again in contrast to the two reference anti-inflammatory compounds, inhibited release concentration-dependently also under these conditions. The concentration of the compound which inhibited exocytosis by 50% was 30-100 microM in normal and 3-10 microM in cytochalasin B-treated neutrophils. The effect of benzydamine and reference compounds on the respiratory burst was tested by assaying for superoxide formation in neutrophils and H2O2 formation in mononuclear phagocytes. Benzydamine was inactive on neutrophils and inhibited slightly the burst response of monocytes and macrophages. Two reference compounds, bufexamac and phenylbutazone, were generally more active. The strongest inhibitory effect was that of phenylbutazone on fMLP-stimulated cells. Benzydamine lacked activity under these conditions, indicating that it does not bind to the receptor of formylated chemotactic peptides.(ABSTRACT TRUNCATED AT 250 WORDS)
D001591:Benzydamine / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000201:enzymology; D005089:Exocytosis / Q000187:drug effects*; D005966:Glucuronidase / Q000097:blood; D006801:Humans; D006861:Hydrogen Peroxide / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D009000:Monocytes / Q000502:physiology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects*; D010586:Phagocytes / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology*; D013481:Superoxides / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011720:Pyrazoles; D013481:Superoxides; D000001:Calcimycin; D003571:Cytochalasin B; D001591:Benzydamine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D005966:Glucuronidase; D013755:Tetradecanoylphorbol Acetate