Expression of CD203c and CD63 in human basophils: relationship to differential regulation of piecemeal and anaphylactic degranulation processes.
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 microm. 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 mum dramatically increased the presence of degranulation sacs, a morphological feature of AND.


CONCLUSIONS
It is proposed that CD63 expression results from only the AND form of histamine release.
MacGlashan
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Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA. dmacglas@jhmi.edu
D000707:Anaphylaxis / Q000276:immunology*; D015703:Antigens, CD / Q000378:metabolism*; D015549:Basophil Degranulation Test; D001491:Basophils / Q000276:immunology*; D015415:Biomarkers; D015550:Cell Degranulation / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006636:Histamine Release / Q000276:immunology*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011755:Pyrophosphatases / Q000378:metabolism*; D060149:Tetraspanin 30
D015703:Antigens, CD; D015415:Biomarkers; C554586:CD63 protein, human; C427944:ENPP3 protein, human; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; C116174:bisindolylmaleimide II; D011493:Protein Kinase C; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; C064758:Ro 31-8220