Adenosine-activated mast cells induce IgE synthesis by B lymphocytes

An A2B-mediated process involving Th2 cytokines IL-4 and IL-13 with implications for asthma

Sergey Ryzhov, Anna E. Goldstein, Anton Matafonov, Dewan Zeng, Italo Biaggioni, Igor Feoktistov

Research output: Contribution to journalArticle

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Abstract

Adenosine provokes bronchoconstriction in asthmatics through acute activation of mast cells, but its potential role in chronic inflammation has not been adequately characterized. We hypothesized that adenosine up-regulates Th2 cytokines in mast cells, thus promoting IgE synthesis by B lymphocytes. We tested this hypothesis in human mast cells (HMC-1) expressing A2A, A2B, and A3 adenosine receptors. The adenosine analog 5′-N-ethylcarboxamidoadenosine (NECA) (10 μM) increased mRNA expression of IL-1β, IL-3, IL-4, IL-8, and IL-13, but not IL-2 and IFN-γ. Up-regulation of IL-4 and IL-13 was verified using RT-PCR and ELISA; 10 μM NECA increased IL-13 concentrations in HMC-1 conditioned medium 28-fold, from 7.6 ± 0.3 to 215 ± 4 pg/ml, and increased IL-4 concentrations 6-fold, from 19.2 ± 0.1 to 117 ± 2 pg/mL. This effect was mediated by A2B receptors because neither the selective A2A agonist 2-p-(2-carboxyethyl)phenethylamino-NECA nor the selective A3 agonist N6-(3-iodobenzyl)-N-methyl-5′ -carbamoyladenosine reproduced it, and the selective A2B antagonist 3-isobutyl-8-pyrrolidinoxanthine prevented it. Constitutive expression of CD40 ligand on HMC-1 surface was not altered by NECA. Human B lymphocytes cocultured for 12 days with NECA-stimulated HMC-1 produced 870 ± 33 pg IgE per 106 B cells, whereas lymphocytes cocultured with nonstimulated HMC-1, or cultured alone in the absence or in the presence of NECA, produced no IgE. Thus, we demonstrated induction of IgE synthesis by the interaction between adenosine-stimulated mast cells and B lymphocytes, and suggest that this mechanism is involved in the amplification of the allergic inflammatory responses associated with asthma.

Original languageEnglish
Pages (from-to)7726-7733
Number of pages8
JournalJournal of Immunology
Volume172
Issue number12
Publication statusPublished - 15 Jun 2004
Externally publishedYes

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Adenosine-5'-(N-ethylcarboxamide)
Interleukin-13
Mast Cells
Interleukin-4
Adenosine
Immunoglobulin E
B-Lymphocytes
Asthma
Cytokines
Adenosine A2B Receptors
Up-Regulation
Adenosine A3 Receptors
Adenosine A2A Receptors
CD40 Ligand
Bronchoconstriction
Interleukin-3
Conditioned Culture Medium
Interleukin-8
Interleukin-1
Interleukin-2

ASJC Scopus subject areas

  • Immunology

Cite this

Adenosine-activated mast cells induce IgE synthesis by B lymphocytes : An A2B-mediated process involving Th2 cytokines IL-4 and IL-13 with implications for asthma. / Ryzhov, Sergey; Goldstein, Anna E.; Matafonov, Anton; Zeng, Dewan; Biaggioni, Italo; Feoktistov, Igor.

In: Journal of Immunology, Vol. 172, No. 12, 15.06.2004, p. 7726-7733.

Research output: Contribution to journalArticle

Ryzhov, S, Goldstein, AE, Matafonov, A, Zeng, D, Biaggioni, I & Feoktistov, I 2004, 'Adenosine-activated mast cells induce IgE synthesis by B lymphocytes: An A2B-mediated process involving Th2 cytokines IL-4 and IL-13 with implications for asthma', Journal of Immunology, vol. 172, no. 12, pp. 7726-7733.
Ryzhov, Sergey ; Goldstein, Anna E. ; Matafonov, Anton ; Zeng, Dewan ; Biaggioni, Italo ; Feoktistov, Igor. / Adenosine-activated mast cells induce IgE synthesis by B lymphocytes : An A2B-mediated process involving Th2 cytokines IL-4 and IL-13 with implications for asthma. In: Journal of Immunology. 2004 ; Vol. 172, No. 12. pp. 7726-7733.
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