Tyrosine phosphorylation and inositol phosphate production: are early events in human eosinophil activation stimulated by immobilized secretory IgA and IgG?
Eosinophils are implicated as major inflammatory cells in parasite infection and allergic reactions. Among various mediators, eosinophil granule cationic proteins play an important role in the pathophysiology of diseases. However, little is known about the actual physiologic stimuli for eosinophil degranulation and the signaling events for triggering eosinophil degranulation. A series of in vivo and in vitro studies suggest that the interaction between antibody coated parasites and Fc receptors on eosinophils is one of the most effective triggers for eosinophil degranulation. Similarly, eosinophil degranulation can be induced in vitro by Sepharose beads coated with human sIgA or IgG. Eosinophil degranulation induced by these stimuli is mediated by PTX-sensitive membrane-bound heterotrimeric G protein(s), and is accompanied by the rapid turnover of inositol phosphates. The production of inositol phosphates is inhibited by PTX. Eosinophil activation by sIgA and IgG also involves tyrosine phosphorylation of several proteins and is inhibited by tyrosine kinase inhibitors. Thus phospholipase C-coupled G protein(s) and tyrosine kinases are key molecules in early signal transduction of eosinophil activation induced by sIgA and IgG. Although further studies are needed to identify which tyrosine kinase(s) is specifically involved in the eosinophil degranulation mechanism, these molecules could be a target for therapies of human diseases where eosinophils are involved.
Kita
H
H
Department of Immunology, Mayo Clinic, Rochester, MN 55905.
Kato
M
M
Gleich
G J
GJ
Abraham
R T
RT
D015550:Cell Degranulation / Q000276:immunology; D004804:Eosinophils / Q000502:physiology*; D019833:Genistein; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000096:biosynthesis* / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000276:immunology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D010738:Type C Phospholipases / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007295:Inositol Phosphates; D007529:Isoflavones; D010750:Phosphoproteins; D010566:Virulence Factors, Bordetella; D019833:Genistein; D011065:Poly(ADP-ribose) Polymerases; D011505:Protein-Tyrosine Kinases; D010738:Type C Phospholipases