Secretory IgA-mediated basophil activation II. Roles of GTP-binding regulatory proteins and phosphatidylinositol 3-kinase

Secretory IgA (sIgA) is the most abundant Ig isotype in mucous secretions i n the upper and lower airways, where basophils exert effector functions dur ing allergic inflammation. We recently demonstrated that immobilized sIgA o n Sepharose beads is capable of inducing basophil degranulation (similar to 15% of total histamine). To investigate the detailed mechanisms of this de granulation, we established in this study a new assay system for sIgA-media ted basophil activation. Immobilized sIgA on a plastic surface induced stro ng histamine release (similar to 50% of total histamine) comparable to anti -IgE, and we analyzed the nature of basophil signal transduction by sIgA us ing various inhibitors. sIgA-induced basophil histamine release was inhibit ed completely by pertussis toxin, but anti-IgE-induced release was not affe cted. sIgA-mediated release was also inhibited by phosphatidylinositol 3-ki nase (PI 3-kinase) inhibitor, wortmannin. These results strongly suggest th at sIgA activates basophils via an IgE-independent novel mechanism involvin g both Gi protein and PI 3-kinase. (C) 1999 Academic Press.