Pharmacology of IgE-mediated desensitization of human basophils: Effects of protein kinase C and Src-family kinase inhibitors

Donald Macglashan, Katsushi Miura, Sandra Lavens-Phillips

Research output: Contribution to journalArticle

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. (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)1717-1727
Number of pages11
JournalBiochemical Pharmacology
Volume60
Issue number11
DOIs
StatePublished - Dec 1 2000

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Basophils
src-Family Kinases
Protein Kinase C
Immunoglobulin E
Pharmacology
Chemical activation
Down-Regulation
Protein C Inhibitor
Protein Kinase Inhibitors
Mast Cells
Pharmaceutical Preparations

Keywords

  • Desensitization
  • Histamine release
  • Human basophils
  • Protein kinase C
  • Src kinases
  • Syk kinase

ASJC Scopus subject areas

  • Pharmacology

Cite this

Pharmacology of IgE-mediated desensitization of human basophils : Effects of protein kinase C and Src-family kinase inhibitors. / Macglashan, Donald; Miura, Katsushi; Lavens-Phillips, Sandra.

In: Biochemical Pharmacology, Vol. 60, No. 11, 01.12.2000, p. 1717-1727.

Research output: Contribution to journalArticle

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