Inhibition of histamine release from human mast cells by natural chymase inhibitors.

AIM To investigate the ability of natural chymase inhibitors to modulate histamine release from human mast cells. METHODS Enzymatically dispersed cells from human lung, tonsil, and skin were challenged with anti-IgE or calcium ionophore A23187 in the absence or presence of the natural chymase inhibitors secretory leukocyte protease inhibitor (SLPI) and alpha(1)-antitrypsin, then histamine release was determined. RESULTS IgE-dependent histamine release from lung, tonsil, and skin mast cells were inhibited by up to 70 %, 61 %, and 62 %, respectively following incubation with alpha(1)-antitrypsin (5000 nmol/L). SLPI 5000 nmol/L was also able to inhibit anti-IgE-dependent histamine released from lung, tonsil and skin mast cells by up to approximately 72 %, 67 %, and 58 %, respectively. While neither alpha(1)-antitrypsin nor SLPI by themselves altered histamine release from lung, tonsil and skin mast cells, they were able to inhibit calcium ionophore-induced histamine release from lung and tonsil mast cells. CONCLUSION Both micro(1)-antitrypsin and SLPI could potently inhibit IgE-dependent and calcium ionophore- induced histamine release from dispersed human lung, tonsil, and skin mast cells in a concentration-dependent manner, which suggested that they were likely to play a protective role in mast cell associated diseases including allergy.