tosylphenylalanyl-chloromethyl-ketone and Anaphylaxis

Adenosine has been shown to enhance mast cell degranulation when added together with an antigen. Such augmentation of mast cell activation is relevant to exacerbation of allergic asthma symptoms. Na-Tosyl-Phe chloromethyl ketone (TPCK) is a chymotrypsine-like chymase inhibitor, which has anti-inflammatory properties. In this study, we investigated the effects of TPCK on mast cell synergistic degranulation induced by antigen and adenosine. Here, we report that TPCK almost completely suppressed enhanced degranulation by inhibiting granule movement. Consistent with this, intraperitoneal administration of TPCK resulted in significant amelioration of passive cutaneous anaphylaxis in mice. Furthermore, we demonstrated that TPCK completely inhibited Thr308 phosphorylation of protein kinase B in mast cells stimulated with antigen and adenosine. These results provide a novel action of TPCK for the prevention of mast cell degranulation induced by antigen and adenosine.

Topics: Adenosine; Anaphylaxis; Animals; Antigens; Cell Degranulation; Cells, Cultured; Chymases; Mast Cells; Mice; Secretory Vesicles; Serine Proteinase Inhibitors; Tosylphenylalanyl Chloromethyl Ketone; Vasodilator Agents