The release of histamine is associated with the inactivation of mast cell chymase during immediate allergic wheal reaction in the skin

Background Chymase released by mast cells can participate in the immediate allergic wheal. However, chymase may be susceptible to inactivation by protease inhibitors during degranulation. Objective To study the inactivation of chymase and the release of histamine in the immediate allergic wheal reaction. Methods Ten sensitive atopic subjects were prick-tested with the cow dander allergen, and skin biopsies were taken from the control skin and from the challenge site at 30 and 120 min. Tryptase (Tact) and chymase (Cact) activities in mast cells were measured enzyme-histochemically. Sequential double-staining was used to demonstrate the activity and immunoreactivity (Cprot) of chymase in the same mast cell as well as alpha (1)-proteinase inhibitor (alpha (1)-PI) and alpha (1)-antichymotrypsin (alpha (1)-AC) in Tact(+) cells. Skin microdialysis was used to monitor histamine release after the allergen challenge for up to 120 min Results The numbers of Tact(+) and Cact(+) cells were already maximally decreased at 30 min by 37 +/- 17% and 61 +/- 31%, respectively (mean +/- SD, P < 0.0001). At the same time the Cact(+)/Cprot(+) ratio decreased from 82 +/- 15% to 43 +/- 16% (P < 0.0001). The cumulative histamine release at 30 min correlated negatively with the Cact(+)/Tact(+) (P = 0.047) and Cact(+)/Cprot(+) (P = 0.024) ratios, but positively with the decrease in the number of Cact(+) cells (P = 0.024). These data indicate that the higher the histamine release the lower the chymase activity. Also the number of Tact(+) cells in the control skin correlated positively with the cumulative histamine release at 120 min (P = 0.043). In the control skin, 95 +/- 6% and 76 +/- 8% of the Tact(+) cells displayed alpha (1)-AC and alpha (1)-PI, respectively. Conclusion In addition to extensive degranulation of mast cells, chymase is also rapidly inactivated after the allergen challenge, possibly by pre-existing chymase inhibitors in the mast cells. This inactivation is associated with the release of histamine