α
1-Antitrypsin, a major proteinase inhibitor in human blood, was found to have an inhibitory effect on the IgE or, Ca
2+ionophore A23187-mediated histamine release from human peripheral leukocytes in a dose-response manner within the range of its physiological concentration in plasma (IC
50: IgE-mediated 2.0mg/ml, A23187-mediated 3.0mg/ml). α
1-Antitrypsin affected histamine release immediately, even after one minute's preincubation with cells before anti-human IgE antibody challenge, and the effect was almost irreversible up to 4 hours incubation after washing out α
1-antitrypsin. The inhibitory effect of α
1-antitrypsin was reversed by adding trypsin. So, it is conceivable that the inhibitory effect of α
1-antitrypsin on histamine release was specific to its proteinase-inhibitor function. α
1-Antitrypsin was found to affect the first Ca
2+-independent step in histamine release and not to affect the second Ca
2+-dependent step. As plasma normally contains 2-3mg/ml of α
1-antitrypsin, we tried to investigate the effect of plasma on Ca
2+-ionophore A23187-mediated histamine release from human leukocytes. But normal human plasma was found to have no effect or did not reverse the inhibitory effect of α
1-antitrypsin added to plasma. It seemed that the effect of α
1-antitrypsin on histamine release was counterated by proteinases in normal human blood. However it is conceivable that in a situation such as inflammation or severe attacks of bronchial asthma, which raise α
1-antitrypsin levels in blood, or in a local lesion, α
1-antitrypsin could affect histamine release from stimulated human basophils or mast cells.
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