[Modulatory effect of bisbenzamidine, a specific inhibitor of tryptase on mast cell secretion]

To study the ability of bisbenzamidine, a specific inhibitor of tryptase, to stabilize mast cells.

Human tonsil tissues were chopped up finely and digested with collagenase and hyaluronidase. Dispersed cells were separated from undigested tissue by filtration through a nylon gauze. Prior to challenge, the cells were resuspended in complete HBSS and aliquots of 100 mL containing 4 x 10(3)-6 x 10(3) mast cells were added to a 100 microL aliquot of anti-IgE, calcium ionophore, bisbenzamidine or complete HBSS and incubated for 15 min at 37 degrees Celsius. The reaction was terminated by addition of 150 microL ice cold HBSS and the tubes centrifuged immediately. Tryptase was quantified by ELISA.

At concentrations of 1 mg/L and 10 mg/L, bisbenzamidine could inhibit spontaneous tryptase release by 47% after 45 min. A 3.2 or 2.6 fold increase in tryptase release was achieved when cells were incubated with 1 g/L anti-IgE antibody or 1 micromol/L calcium ionophore for 15 min at 37 degrees Celsius. A dose dependent inhibition of tryptase release induced by anti-IgE antibody was observed when dispersed tonsil cells were treated with bisbenzamidine.

Bisbenzamidine can inhibit IgE-dependent tryptase release from human tonsil mast cells. Therefore, it seems likely that this inhibitor of tryptase is a novel promising mast cell stabilizing drug for treating and preventing allergic inflammation or other mast cell associated diseases.