Anaphylactic relase of a basophil kallikrein-like activity. II. A mediator of immediate hypersensitivity reactions.

A C T This report describes the immune release of a new mediator from human peripheral leukocytes, a basophil kallikrein-like activity (BK-A).The release process is initiated by the interaction of antigen or anti-IgE with cell-bound IgE, and appears to be similar in mechanism to the release of histamine and other mediators of the immediate hypersensitivity reaction.The dose-response relationships arid kinetics ofhistamine and BK-A release from antigen-challenged peripheral leukocytes are similar.The release of the BK-A is calcium and temperature dependent, requires metabolic energy, and is controlled by hormone-receptor interactions that influence the cellular level of cyclic AMP, as has been described for other mediators of immediate hypersensitivity reactions.The data indicate that the interaction of BK-A with human plasma kininogen, generates immunoreactive kinin.We con- clude that the antigen-IgE interaction leads to the release from human basophils of a new mediator, a basophil kallikrein-like activity which may well be a link between reactions of immediate hypersensitivity and the plasma and/or tissue kinin-generating systems. METHODS Materials. The p-toluenesulfonyl-L-arginine [3HJmethyl ester ([H]TAMe) (210 mCi/mmol) was purchased from Bio- chemical and Nuclear Corp. Burbank, Calif.Tris buffers used in the release of histamine and the arginine esterase from basophils were made of 0.025 M preset Tris, pH 7.35 at 37°C (Sigma Chemical Co., St. Louis, Mo.), 0.12 M sodium chloride, 5 mM potassium chloride, and 0.03% human serum albumin (Behring-Werke, Marburg/Lahn, West Germany).The above constitutes Tris-A; Tris-ACM contains, in addi- tion, calcium 0.6 mM and magnesium 1.0 mM (3).The fol- lowing were purchased from Schwarz/Mann Div., Becton, Dickinson & Co., Orangeburg, N. Y.: TAMe and Tris from which the buffer used in the [3H]TAMe basophil arginine esterase assay was made (0.06 M), and adjusted with HCl to pH 8.0 at 25°C.Theophylline, histamine, isoproterenol, and colchicine were purchased from the Sigma Chemical Co.; diatrizoate sodium (Hypaque) from Winthrop Labora- tories, New York; Ficoll from Pharmacia Fine Chemicals, Div.