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.