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 in the upper and lower airways, where basophils exert effector functions during allergic inflammation. We recently demonstrated that immobilized sIgA on Sepharose beads is capable of inducing basophil degranulation ( approximately 15% of total histamine). To investigate the detailed mechanisms of this degranulation, we established in this study a new assay system for sIgA-mediated basophil activation. Immobilized sIgA on a plastic surface induced strong histamine release ( approximately 50% of total histamine) comparable to anti-IgE, and we analyzed the nature of basophil signal transduction by sIgA using various inhibitors. sIgA-induced basophil histamine release was inhibited completely by pertussis toxin, but anti-IgE-induced release was not affected. sIgA-mediated release was also inhibited by phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, wortmannin. These results strongly suggest that sIgA activates basophils via an IgE-independent novel mechanism involving both Gi protein and PI 3-kinase.
Iikura
M
M
Department of Allergy and Rheumatology, Department of Respiratory Medicine, Department of Bioregulatory Function, University of Tokyo Graduate School of Medicine, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Yamaguchi
M
M
Miyamasu
M
M
Morita
Y
Y
Iwase
T
T
Moro
I
I
Yamamoto
K
K
Hirai
K
K
D001491:Basophils / Q000187:drug effects / Q000276:immunology*; D015550:Cell Degranulation; D004797:Enzyme-Linked Immunosorbent Assay; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006636:Histamine Release; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*
D007071:Immunoglobulin A, Secretory; D019869:Phosphatidylinositol 3-Kinases; D019204:GTP-Binding Proteins