Marked differences in the signaling requirements for expression of CD203c and CD11b versus CD63 expression and histamine release in human basophils.
Many techniques are being used to examine the status of circulating human basophils including the enhanced expression of a variety of cell surface proteins. There is accumulating evidence that there are at least two compartments containing these activation marker proteins but there are only some indications for the signaling requirements for each of the compartments. This study began with published reports by other investigators who potentially dissociated CD63 expression from anaphylactic degranulation with the p38 inhibitor, SB203580, a possible falsification of a previously proposed hypothesis regarding CD63 expression. To explore the signaling requirements for CD63, a variety of pharmacological agents were used to inhibit or enhance 4 endpoints of basophil activation. First, it was found that inhibition of both histamine release and CD63 expression with SB203580 was concordant. But it was also found that this agent had no effect on increased expression of CD203c and CD11b. Actin polymerization inhibitors caused marked enhancement of CD63 expression (concordant with their effects on degranulation) with no effect on expression of CD203c and CD11b. The third generation syk inhibitor, NVP-QAB205, showed a 5-fold lower potency for inhibiting expression of CD203c and CD11b than for CD63. Finally, while desensitization of CD11b and CD203c expression occurs, it is slower than desensitization of the CD63 response. Taken together, these various observations demonstrate a marked difference in the early signaling requirements for the CD11b/CD203c compartment and CD63 degranulation and provide support for the hypothesis that CD11b and CD203c reside in a similar compartment.
Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA. dmacglas @ jhmi.edu
Donald
D
MacGlashan
D000199:Actins / Q000037:antagonists & inhibitors; D015549:Basophil Degranulation Test; D001491:Basophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D039481:CD11b Antigen / Q000235:genetics* / Q000276:immunology; D015550:Cell Degranulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D006632:Histamine / Q000276:immunology / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors; D010727:Phosphoric Diester Hydrolases / Q000235:genetics* / Q000276:immunology; D058105:Polymerization / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology; D011755:Pyrophosphatases / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D000072377:Syk Kinase; D060149:Tetraspanin 30 / Q000235:genetics* / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors
D000199:Actins; D039481:CD11b Antigen; C427944:ENPP3 protein, human; C509295:ITGAM protein, human; D007093:Imidazoles; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D060149:Tetraspanin 30; D006632:Histamine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; D048051:p38 Mitogen-Activated Protein Kinases; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; C093642:SB 203580