Expression of CD203c and CD63 in human basophils: Relationship to differential regulation of piecemeal and anaphylactic degranulation processes

Research output: Contribution to journalArticle

Abstract

Background Activation of human basophils results in the release of many different mediators and the expression of new cell surface proteins. The markers CD63 and CD203c have been used in recent years to assess basophil activation but there have been many studies that demonstrate that expression of these markers can be dissociated from histamine release. Objective To determine the signal transduction requirements for CD203c and CD63 expression. Methods The current study began by exploring the dependency of CD203c and CD63 expression on protein kinase C (PKC) using known selective inhibitors of PKC. Results Between 30 and 300 nm, Ro-31-8220 and bisindoylmaleimide II (Bis II) had no effect on formyl-met-leu-phe- or anti-IgE-induced CD63 or CD203c but enhanced IgE-mediated expression of CD63 by an average of 15-fold at concentrations >1 μm. These results led to the suggestion that these inhibitors altered the normal pathways of degranulation (by a non-PKC dependent mechanism), shifting the normal presence of piecemeal degranulation to the process termed anaphylactic degranulation (AND). Morphological studies demonstrated that concentrations of Ro-31-8220 and Bis II>1 μm dramatically increased the presence of degranulation sacs, a morphological feature of AND. Conclusion It is proposed that CD63 expression results from only the AND form of histamine release.

Original languageEnglish (US)
Pages (from-to)1365-1377
Number of pages13
JournalClinical and Experimental Allergy
Volume40
Issue number9
DOIs
StatePublished - Sep 2010

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Basophils
Histamine Release
Protein Kinase C
methionyl-leucyl-phenylalanine
Immunoglobulin E
Signal Transduction
Membrane Proteins
Phosphotransferases
Ro 31-8220
anti-IgE antibodies

Keywords

  • activation marker
  • calcium
  • histamine release
  • protein kinase C

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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title = "Expression of CD203c and CD63 in human basophils: Relationship to differential regulation of piecemeal and anaphylactic degranulation processes",
abstract = "Background Activation of human basophils results in the release of many different mediators and the expression of new cell surface proteins. The markers CD63 and CD203c have been used in recent years to assess basophil activation but there have been many studies that demonstrate that expression of these markers can be dissociated from histamine release. Objective To determine the signal transduction requirements for CD203c and CD63 expression. Methods The current study began by exploring the dependency of CD203c and CD63 expression on protein kinase C (PKC) using known selective inhibitors of PKC. Results Between 30 and 300 nm, Ro-31-8220 and bisindoylmaleimide II (Bis II) had no effect on formyl-met-leu-phe- or anti-IgE-induced CD63 or CD203c but enhanced IgE-mediated expression of CD63 by an average of 15-fold at concentrations >1 μm. These results led to the suggestion that these inhibitors altered the normal pathways of degranulation (by a non-PKC dependent mechanism), shifting the normal presence of piecemeal degranulation to the process termed anaphylactic degranulation (AND). Morphological studies demonstrated that concentrations of Ro-31-8220 and Bis II>1 μm dramatically increased the presence of degranulation sacs, a morphological feature of AND. Conclusion It is proposed that CD63 expression results from only the AND form of histamine release.",
keywords = "activation marker, calcium, histamine release, protein kinase C",
author = "Donald Macglashan",
year = "2010",
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language = "English (US)",
volume = "40",
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N2 - Background Activation of human basophils results in the release of many different mediators and the expression of new cell surface proteins. The markers CD63 and CD203c have been used in recent years to assess basophil activation but there have been many studies that demonstrate that expression of these markers can be dissociated from histamine release. Objective To determine the signal transduction requirements for CD203c and CD63 expression. Methods The current study began by exploring the dependency of CD203c and CD63 expression on protein kinase C (PKC) using known selective inhibitors of PKC. Results Between 30 and 300 nm, Ro-31-8220 and bisindoylmaleimide II (Bis II) had no effect on formyl-met-leu-phe- or anti-IgE-induced CD63 or CD203c but enhanced IgE-mediated expression of CD63 by an average of 15-fold at concentrations >1 μm. These results led to the suggestion that these inhibitors altered the normal pathways of degranulation (by a non-PKC dependent mechanism), shifting the normal presence of piecemeal degranulation to the process termed anaphylactic degranulation (AND). Morphological studies demonstrated that concentrations of Ro-31-8220 and Bis II>1 μm dramatically increased the presence of degranulation sacs, a morphological feature of AND. Conclusion It is proposed that CD63 expression results from only the AND form of histamine release.

AB - Background Activation of human basophils results in the release of many different mediators and the expression of new cell surface proteins. The markers CD63 and CD203c have been used in recent years to assess basophil activation but there have been many studies that demonstrate that expression of these markers can be dissociated from histamine release. Objective To determine the signal transduction requirements for CD203c and CD63 expression. Methods The current study began by exploring the dependency of CD203c and CD63 expression on protein kinase C (PKC) using known selective inhibitors of PKC. Results Between 30 and 300 nm, Ro-31-8220 and bisindoylmaleimide II (Bis II) had no effect on formyl-met-leu-phe- or anti-IgE-induced CD63 or CD203c but enhanced IgE-mediated expression of CD63 by an average of 15-fold at concentrations >1 μm. These results led to the suggestion that these inhibitors altered the normal pathways of degranulation (by a non-PKC dependent mechanism), shifting the normal presence of piecemeal degranulation to the process termed anaphylactic degranulation (AND). Morphological studies demonstrated that concentrations of Ro-31-8220 and Bis II>1 μm dramatically increased the presence of degranulation sacs, a morphological feature of AND. Conclusion It is proposed that CD63 expression results from only the AND form of histamine release.

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