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.

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 A(2A), A(2B), and A(3) adenosine receptors. The adenosine analog 5'-N-ethylcarboxamidoadenosine (NECA) (10 microM) increased mRNA expression of IL-1beta, IL-3, IL-4, IL-8, and IL-13, but not IL-2 and IFN-gamma. Up-regulation of IL-4 and IL-13 was verified using RT-PCR and ELISA; 10 microM 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 A(2B) receptors because neither the selective A(2A) agonist 2-p-(2-carboxyethyl)phenethylamino-NECA nor the selective A(3) agonist N(6)-(3-iodobenzyl)-N-methyl-5'-carbamoyladenosine reproduced it, and the selective A(2B) 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 10(6) 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.

• Authors: Sergey Ryzhov, Anna E Goldstein, Anton Matafonov, Dewan Zeng, Italo Biaggioni, Igor Feoktistov
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 172 Issue 12 Pg. 7726-33 (Jun 15 2004) ISSN: 0022-1767 [Print] United States
• PMID: 15187156 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Cytokines
• Interleukin-13
• RNA, Messenger
• Receptor, Adenosine A2B
• Interleukin-4
• Adenosine-5'-(N-ethylcarboxamide)
• Immunoglobulin E
• Adenosine

Topics

• Adenosine (pharmacology)
• Adenosine-5'-(N-ethylcarboxamide) (pharmacology)
• Asthma (etiology)
• B-Lymphocytes (immunology, physiology)
• Cell Communication (immunology)
• Cells, Cultured
• Coculture Techniques
• Cytokines (genetics)
• Humans
• Immunoglobulin E (biosynthesis)
• Interleukin-13 (immunology)
• Interleukin-4 (immunology)
• Mast Cells (immunology, physiology)
• RNA, Messenger (biosynthesis)
• Receptor, Adenosine A2B (physiology)
• Th2 Cells (immunology)
• Up-Regulation (immunology)