IgE-dependent and IgE-independent stimulation of human basophils increases the presence of immature FcεRIα by reversing degradative pathways

Asifa K. Zaidi, Donald MacGlashan

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Expression of the high-affinity IgE receptor, FcRI, on mast cells and basophils has previously been shown to be sensitive to the presence of IgE or cytokines. The current study examined whether stimulation of human basophils resulted in a change in the expression of FcRI. Methods: Changes in the well-expressed immature intracellular form of the receptor, FcRIα (p46), were examined by quantitative PCR, Western blot and the pulse-chase method. Results: Both IgE-dependent (anti-IgE antibody) and IgE-independent stimulation [formyl-methionyl-leucyl-phenylalanine (FMLP) and C5a] led to increased accumulation of p46. The p46 form of FcRIα increased 1.52 ± 0.09-, 2.58 ± 0.09- and 1.47 ± 0.07-fold following stimulation with anti-IgE, FMLP and C5a, respectively. There were no changes in the steady-state levels of mRNA for FcRIα. The kinetics of the increase in p46 was slow following stimulation with anti-IgE antibody, with the earliest increases observed after 8 h. The p46 form was degraded in a bafilomycin A (lysosomal inhibitor)-sensitive process. There was no synergy between treatment with bafilomycin A and anti-IgE or FMLP stimulation, suggesting that the 2 methods of enhancement operate on the same pathway. Pulse-chase studies corroborated this conclusion. In contrast, IL-3 and bafilomycin A synergistically increased p46, suggesting that IL-3 increased synthesis of FcRIα. Conclusions: Taken together, these results suggest that secretagogue stimulation results in an increase in p46 due to reversal of degradative pathways rather than increased synthesis of FcRIα. Nevertheless, a decrease in the degradation of FcRIα at an intermediate step in its processing by non-FcRI-dependent stimulation may still influence expression of this important receptor.

Original languageEnglish (US)
Pages (from-to)15-24
Number of pages10
JournalInternational Archives of Allergy and Immunology
Volume154
Issue number1
DOIs
StatePublished - Dec 1 2010

Keywords

  • IgE
  • IgE receptor
  • Receptor processing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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