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Clinical and Developmental Immunology
Volume 2013 (2013), Article ID 764395, 17 pages
http://dx.doi.org/10.1155/2013/764395
Research Article

Altered Sympathetic-to-Immune Cell Signaling via β2-Adrenergic Receptors in Adjuvant Arthritis

1Hoover Arthritis Research Center, Banner Health Research Institute, 10515 W. Santa Fe Drive, Sun City, AZ 85351, USA
2Department of Psychology, Kent State University, 133 Kent Hall, Kent, OH 44242, USA
3Kent-Summa Institute for Clinical and Translational Research, Summa Health System, 525 East Market Street, Akron,OH 44304, USA
4Department of Pathology and Human Anatomy, Alumni Hall for Basic Sciences, Loma Linda University School of Medicine, 11021 Campus Street, Loma Linda, CA 92354, USA

Received 4 May 2013; Accepted 2 August 2013

Academic Editor: Jianying Zhang

Copyright © 2013 Dianne Lorton et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Adjuvant-induced arthritic (AA) differentially affects norepinephrine concentrations in immune organs, and in vivo β-adrenergic receptor (β-AR) agonist treatment distinctly regulates ex vivo cytokine profiles in different immune organs. We examined the contribution of altered β-AR functioning in AA to understand these disparate findings. Twenty-one or 28 days after disease induction, we examined β2-AR expression in spleen and draining lymph nodes (DLNs) for the arthritic limbs using radioligand binding and western blots and splenocyte β-AR-stimulated cAMP production using enzyme-linked immunoassay (EIA). During severe disease, β-AR agonists failed to induce splenocyte cAMP production, and β-AR affinity and density declined, indicating receptor desensitization and downregulation. Splenocyte β2-AR phosphorylation (pβ2-AR) by protein kinase A (pβ2-ARPKA) decreased in severe disease, and pβ2-AR by G protein-coupled receptor kinases (pβ2-ARGRK) increased in chronic disease. Conversely, in DLN cells, pβ2-ARPKA rose during severe disease, but fell during chronic disease, and pβ2-ARGRK increased during both disease stages. A similar pβ2-AR pattern in DLN cells with the mycobacterial cell wall component of complete Freund’s adjuvant suggests that pattern recognition receptors (i.e., toll-like receptors) are important for DLN pβ2-AR patterns. Collectively, our findings indicate lymphoid organ- and disease stage-specific sympathetic dysregulation, possibly explaining immune compartment-specific differences in β2-AR-mediated regulation of cytokine production in AA and rheumatoid arthritis.