ROLE OF TYROSINE KINASES IN HUMAN EOSINOPHIL DEGRANULATION

Degranulation of eosinophils and subsequent release of toxic granule p roteins play a key role in allergic diseases such as bronchial asthma. However, little is known about the intracellular signaling mechanism of eosinophil degranulation. In this report, we investigated the role of protein tyrosine kinases (PTK) in the degranulation of human periph eral blood eosinophils. Stimulation of eosinophils with Sepharose bead s coated with secretory IgA (sIgA) or IgG triggered the phosphorylatio n of tyrosine residues in several proteins, including 50-65, 73, 78, 1 00, 105 and 113 kD. In addition, IgG-coated beads induced a rapid incr ease in the tyrosine kinase activity of src-like PTK, Fgr. The tyrosin e kinase inhibitors, genistein and herbimycin A, inhibited both the ty rosine phosphorylation and degranulation responses of eosinophils indu ced by sIgA- or IgG-coated beads. In contrast, eosinophil degranulatio n induced by phorbol myristate acetate was not affected by genistein. These findings suggest that a PTK-dependent signaling pathway plays an important role in triggering the eosinophil degranulation induced by immobilized immunoglobulin.