Post-receptorial mechanisms underlie functional disregulation of beta2-adrenergic receptors in lymphocytes from Multiple Sclerosis patients

J Neuroimmunol. 2004 Oct;155(1-2):143-9. doi: 10.1016/j.jneuroim.2004.05.013.

Abstract

Increased density of beta2-adrenergic receptors has been demonstrated on peripheral blood mononuclear cells (PBMCs) from Multiple Sclerosis (MS) patients. In this study we found that isoproterenol reduces T-cell proliferation and IFNgamma secretion in PBMCs cultures from healthy controls and IFNbeta-treated but not untreated MS patients. Reduced expression levels of G protein coupled receptor kinase (GRK)2/3 (p < 0.05) and increased isoproterenol-induced cAMP accumulation (p < 0.0001) were found in PBMCs from all MS patients. Dibutyryl cAMP reduced the proliferation of PBMCs from all subgroups but in a slighter manner in untreated MS patients. We conclude that signalling through beta2-adrenergic receptors is chronically up-regulated but functionally uncoupled to immunoregulatory functions of lymphocytes from MS patients. Disregulation downstream the cAMP-associated signalling may underlie such a phenomenon.

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Adult
  • Bucladesine / pharmacology
  • Cell Division / drug effects
  • Cell Division / immunology
  • Cyclic AMP / metabolism
  • Cyclic AMP-Dependent Protein Kinase Type II
  • Cyclic AMP-Dependent Protein Kinases / drug effects
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Female
  • Humans
  • Interferon-gamma / drug effects
  • Interferon-gamma / metabolism
  • Isoproterenol / pharmacology
  • Lymphocytes / drug effects
  • Lymphocytes / immunology*
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / metabolism
  • Multiple Sclerosis / physiopathology
  • Neuroimmunomodulation / drug effects
  • Neuroimmunomodulation / immunology*
  • Receptors, Adrenergic, beta-2 / drug effects
  • Receptors, Adrenergic, beta-2 / immunology*
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Up-Regulation / drug effects
  • Up-Regulation / immunology
  • beta-Adrenergic Receptor Kinases

Substances

  • Adrenergic beta-Agonists
  • Receptors, Adrenergic, beta-2
  • Bucladesine
  • Interferon-gamma
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinase Type II
  • Cyclic AMP-Dependent Protein Kinases
  • beta-Adrenergic Receptor Kinases
  • Isoproterenol