Signal transduction in activation of human eosinophils: G protein-dependent and -independent pathways.
Degranulation of eosinophils and subsequent release of toxic granule proteins play a key role in allergic diseases such as bronchial asthma. We have previously shown that stimulation of eosinophils with immobilized secretory immunoglobulin A (sIgA) induced the phosphorylation of several proteins including 51-, 65-, 73-, 78-, 100-, 105- and 113-kD proteins. Pervanadate, a protein tyrosine phosphatase inhibitor, also induced at least 7 tyrosine phosphorylated proteins including those observed with immobilized sIgA. Pervanadate also induced inositol phosphate (IP) production and degranulation of eosinophils in a concentration-dependent manner. Eosinophil production of IP and degranulation as well as tyrosine phosphorylation of proteins induced by sIgA were completely inhibited by a tyrosine kinase inhibitor, genistein, and pertussis toxin (PTX), suggesting the involvement of both the PTX-sensitive guanine 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. Furthermore, pervanadate-induced IP production was partially inhibited by PTX. Finally, a phospholipase C-gamma2 isoform was tyrosine phosphorylated by pervanadate, but not by sIgA. These findings suggest that at least two different pathways, i.e. PTK-mediated G protein-dependent or -independent PLC activation, are involved in the activation of human eosinophils.
Department of Pediatrics, Gunma University School of Medicine, Maebashi, Gunma, Japan. mkato@sb.gunma-u.ac.jp
M
M
Kato
H
H
Kita
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K
Tokuyama
A
A
Morikawa
D001249:Asthma / Q000209:etiology; D015550:Cell Degranulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology*; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis; D007527:Isoenzymes / Q000378:metabolism; D037342:Pertussis Toxin; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007071:Immunoglobulin A, Secretory; D007295:Inositol Phosphates; D007527:Isoenzymes; D010566:Virulence Factors, Bordetella; C076715:pervanadate; D014638:Vanadates; D014443:Tyrosine; D019833:Genistein; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins