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Pharmacology of IgE-mediated desensitization of human basophils: effects of protein kinase C and src-family kinase inhibitors.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 2000 Dec 01; Vol. 60 (11), pp. 1717-27. - Publication Year :
- 2000
-
Abstract
- IgE-mediated down-regulation of secretion from basophils and mast cells is an important component of the overall cellular response that determines the ultimate extent of mediator release. The down-regulatory process that occurs during active secretion has also been associated with the methodological phenomenon called desensitization, but the mechanisms underlying desensitization are not understood. A variety of studies have suggested that activation of protein kinase C (PKC) results in down-regulation of IgE-mediated secretion so we have examined the effect of the PKC inhibitors Ro-31-8220 (3-[1-[3-amidinothio)propyl-1H-indol-3-yl]-3-(1-methyl-1H-indol-3- yl) maleimide) and bis-indolylmaleimide II on desensitization in human basophils. At concentrations that have been shown previously to inhibit PKC-mediated functions in basophils completely, these two drugs had no effect on IgE-mediated desensitization. We did find, however, that the src-family kinase inhibitors PP1 [4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine] and PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3, 4-d]pyrimidine] inhibited desensitization as well as secretion. These data suggest that PKC has little role in down-regulating the IgE-mediated basophil response. However, like the activation signaling cascade, the desensitization process is dependent on the activation of src family kinases.
- Subjects :
- Basophils enzymology
Basophils immunology
Carrier Proteins pharmacology
Desensitization, Immunologic
Dose-Response Relationship, Drug
Histamine Release drug effects
Humans
Hypersensitivity, Immediate immunology
Precipitin Tests
Protein Kinase C metabolism
Protein-Tyrosine Kinases antagonists & inhibitors
Pyrazoles pharmacology
Pyrimidines pharmacology
src-Family Kinases metabolism
Basophils drug effects
Enzyme Inhibitors pharmacology
Hypersensitivity, Immediate enzymology
Intracellular Signaling Peptides and Proteins
Protein Kinase C antagonists & inhibitors
src-Family Kinases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0006-2952
- Volume :
- 60
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 11077055
- Full Text :
- https://doi.org/10.1016/s0006-2952(00)00490-1