SIGNAL-TRANSDUCTION IN ACTIVATION OF HUMAN EOSINOPHILS - G-PROTEIN-DEPENDENT AND G-PROTEIN-INDEPENDENT PATHWAYS

Degranulation of eosinophils and subsequent release of toxic granule p roteins play a key role in allergic diseases such as bronchial asthma. We have previously shown that stimulation of eosinophils with immobil ized secretory immunoglobulin A (sIgA) induced the phosphorylation of several proteins including 51-, 65-, 73-, 78-, 100-, 105- and 113-kD p roteins. Pervanadate, a protein tyrosine phosphatase inhibitor, also i nduced at least 7 tyrosine phosphorylated proteins including those obs erved with immobilized sIgA. Pervanadate also induced inositol phospha te (IP) production and degranulation of eosinophils in a concentration -dependent manner. Eosinophil production of IP and degranulation as we ll as tyrosine phosphorylation of proteins induced by sIgA were comple tely inhibited by a tyrosine kinase inhibitor, genistein, and pertussi s toxin (PTX), suggesting the involvement of both the PTX-sensitive gu anine nucleotide-binding (G) protein and protein tyrosine kinases (PTK ) in sIgA-induced activation of eosinophils. In contrast, PTX did not affect tyrosine phosphorylation induced by sIgA or pervanadate. Furthe rmore, pervanadate-induced IP production was partially inhibited by PT X. Finally, a phospholipase C-gamma 2 isoform was tyrosine phosphoryla ted by pervanadate, but not by sIgA. These findings suggest that at le ast two different pathways, i.e. PTK-mediated G protein-dependent or - independent PLC activation, are involved in the activation of human eo sinophils.