Role of tyrosine kinases in human eosinophil degranulation.
Degranulation of eosinophils and subsequent release of toxic granule proteins 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 peripheral blood eosinophils. Stimulation of eosinophils with Sepharose beads coated with secretory IgA (sIgA) or IgG triggered the phosphorylation of tyrosine residues in several proteins, including 50-65, 73, 78, 100, 105 and 113 kD. In addition, IgG-coated beads induced a rapid increase in the tyrosine kinase activity of src-like PTK, Fgr. The tyrosine kinase inhibitors, genistein and herbimycin A, inhibited both the tyrosine phosphorylation and degranulation responses of eosinophils induced by sIgA- or IgG-coated beads. In contrast, eosinophil degranulation 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.
Kato
M
M
Department of Pediatrics, Gunma University School of Medicine, Maebashi, Japan.
Kita
H
H
Morikawa
A
A
D016227:Benzoquinones; D015550:Cell Degranulation; D004791:Enzyme Inhibitors; D004804:Eosinophils / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology*; D047029:Lactams, Macrocyclic; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D019061:src-Family Kinases
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D007136:Immunoglobulins; D047029:Lactams, Macrocyclic; D011518:Proto-Oncogene Proteins; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D011505:Protein-Tyrosine Kinases; C053102:proto-oncogene proteins c-fgr; D019061:src-Family Kinases