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Regulation of IgE-mediated signalling in human basophils by CD32b and its role in Syk down-regulation: basic mechanisms in allergic disease.
Clin Exp Allergy 2014; 44(5):713-23CE

Abstract

BACKGROUND

CD32b has been previously demonstrated to modulate IgE-mediated secretion from human basophils. However, exploration of the implications of this regulation has been limited. One unstudied area is whether regulation of signalling by CD32 also alters some of the phenotypic changes induced by IgE-mediated activation. The reported character of CD32-mediated signal transduction is not clear for human basophils and the two primary mechanisms considered important in this reaction predict different long-term outcomes, notably predicting different outcomes for down-regulation of syk expression.

OBJECTIVE

Syk expression was considered a unique point of phenotypic control in human basophils and the role of CD32b in its regulation is explored in this study. However, initial pilot studies discovered that IL-3 could markedly up-regulate CD32 expression and first describing the consequences of this up-regulation became an additional focus of this study.

METHODS

Human basophils were examined for the changes in IgE-mediated signalling during simultaneous engagement of CD32b.

RESULTS

Preliminary experiments noted that CD32b could be up-regulated by IL-3 (3- to 12-fold). Both natural variation and induced up-regulation of CD32b modulated the efficacy of this receptor to inhibit IgE-mediated release. Signalling induced by engagement of CD32b (lyn, syk, SHP-1, or SHIP1 phosphorylation) was more consistent with a mode of action involving SHIP1 rather than SHP-1. IgE-mediated down-regulation of syk expression was not altered by co-engagement of CD32b, a result also consistent with a SHIP1-dependent mechanism of inhibition.

CONCLUSIONS

Taken together these results suggest that the combined action of IgE and IgG could generate a natural mechanism, whereby the significant variation in syk expression in allergic subjects occurs without necessarily also inducing mediator release.

Authors+Show Affiliations

Johns Hopkins Asthma and Allergy Center, Baltimore, MD, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24734927

Citation

Macglashan, D, et al. "Regulation of IgE-mediated Signalling in Human Basophils By CD32b and Its Role in Syk Down-regulation: Basic Mechanisms in Allergic Disease." Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, vol. 44, no. 5, 2014, pp. 713-23.
Macglashan D, Moore G, Muchhal U. Regulation of IgE-mediated signalling in human basophils by CD32b and its role in Syk down-regulation: basic mechanisms in allergic disease. Clin Exp Allergy. 2014;44(5):713-23.
Macglashan, D., Moore, G., & Muchhal, U. (2014). Regulation of IgE-mediated signalling in human basophils by CD32b and its role in Syk down-regulation: basic mechanisms in allergic disease. Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology, 44(5), pp. 713-23. doi:10.1111/cea.12155.
Macglashan D, Moore G, Muchhal U. Regulation of IgE-mediated Signalling in Human Basophils By CD32b and Its Role in Syk Down-regulation: Basic Mechanisms in Allergic Disease. Clin Exp Allergy. 2014;44(5):713-23. PubMed PMID: 24734927.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of IgE-mediated signalling in human basophils by CD32b and its role in Syk down-regulation: basic mechanisms in allergic disease. AU - Macglashan,D,Jr AU - Moore,G, AU - Muchhal,U, PY - 2013/03/01/received PY - 2013/05/27/revised PY - 2013/06/06/accepted PY - 2014/4/17/entrez PY - 2014/4/17/pubmed PY - 2014/12/15/medline KW - FceRI KW - immunoregulation KW - signal transduction SP - 713 EP - 23 JF - Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology JO - Clin. Exp. Allergy VL - 44 IS - 5 N2 - BACKGROUND: CD32b has been previously demonstrated to modulate IgE-mediated secretion from human basophils. However, exploration of the implications of this regulation has been limited. One unstudied area is whether regulation of signalling by CD32 also alters some of the phenotypic changes induced by IgE-mediated activation. The reported character of CD32-mediated signal transduction is not clear for human basophils and the two primary mechanisms considered important in this reaction predict different long-term outcomes, notably predicting different outcomes for down-regulation of syk expression. OBJECTIVE: Syk expression was considered a unique point of phenotypic control in human basophils and the role of CD32b in its regulation is explored in this study. However, initial pilot studies discovered that IL-3 could markedly up-regulate CD32 expression and first describing the consequences of this up-regulation became an additional focus of this study. METHODS: Human basophils were examined for the changes in IgE-mediated signalling during simultaneous engagement of CD32b. RESULTS: Preliminary experiments noted that CD32b could be up-regulated by IL-3 (3- to 12-fold). Both natural variation and induced up-regulation of CD32b modulated the efficacy of this receptor to inhibit IgE-mediated release. Signalling induced by engagement of CD32b (lyn, syk, SHP-1, or SHIP1 phosphorylation) was more consistent with a mode of action involving SHIP1 rather than SHP-1. IgE-mediated down-regulation of syk expression was not altered by co-engagement of CD32b, a result also consistent with a SHIP1-dependent mechanism of inhibition. CONCLUSIONS: Taken together these results suggest that the combined action of IgE and IgG could generate a natural mechanism, whereby the significant variation in syk expression in allergic subjects occurs without necessarily also inducing mediator release. SN - 1365-2222 UR - https://www.unboundmedicine.com/medline/citation/24734927/Regulation_of_IgE_mediated_signalling_in_human_basophils_by_CD32b_and_its_role_in_Syk_down_regulation:_basic_mechanisms_in_allergic_disease_ L2 - https://doi.org/10.1111/cea.12155 DB - PRIME DP - Unbound Medicine ER -