In vitro anticholinergic drugs affect CD8+ peripheral blood T-cells apoptosis in COPD

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RESEARCH PRODUCT

In vitro anticholinergic drugs affect CD8+ peripheral blood T-cells apoptosis in COPD

Angela Marina Montalbano Maria Ferraro Mirella Profita Stefania Gerbino Giusy Daniela Albano Loredana Riccobono Mark Gjomarkaj Anna Bonanno Paola Casarosa Michael P. Pieper

subject

Male Immunology Scopolamine Derivatives Apoptosis CD8-Positive T-Lymphocytes Pharmacology Systemic inflammation Cholinergic Antagonists Choline Choline O-Acetyltransferase Pulmonary Disease Chronic Obstructive Annexin Muscarinic acetylcholine receptor medicine Humans Immunology and Allergy Lymphocyte Count Tiotropium Bromide Caspase Aged Receptor Muscarinic M3 Caspase 8 COPD biology Caspase 3 Systemic inflammation Non-neuronal components of cholinergic system Caspases NF B pathway business.industry NF-kappa B Hematology Tiotropium bromide Middle Aged medicine.disease respiratory tract diseases Enzyme Activation Apoptosis biology.protein Female medicine.symptom business Acetylcholine Protein Binding Signal Transduction medicine.drug

description

Novel pharmacological strategies are aimed at the resolution of systemic inflammation in COPD potentiating peripheral blood T-cell (PBT-cell) apoptosis. Although muscarinic acetylcholine receptors (mAChRs) M(3) and choline-acetyltransferase (ChAT) participate in the airway inflammation of COPD, their role in PBT-cell apoptosis remains unexplained. We evaluated in PBT-cells from COPD patients, smoker (S) and control (C) subjects: (1) apoptosis (by annexin V binding), (2) mAChR M(3) and ChAT expression, acetylcholine (ACh)-binding; (3) choline levels in serum and PBT-cells extracts. We tested the effects of Tiotropium (Spiriva(®)) and hemicholinium-3 (HCh-3) on apoptosis, NFκB pathway, caspases 3 and 8 activity and choline levels, in PBT-cells from COPD patients. We showed that: (1) apoptosis, mAChR M(3) and ChAT expression and the CD3+ and CD8+ ACh-binding are increased in PBT-cells from COPD patients when compared to C subjects, while CD4+/CD8+ ratio of ACh-binding to PBT cells was reduced in COPD; (2) choline levels are higher in serum and PBT-cells extracts from COPD patients than in S and C; (3) Tiotropium and HCh-3 reduced CD4+ and increased CD8+ apoptosis via caspases 3 and 8 activities and via IκB mediated mechanisms in COPD patients. This study suggests the involvement of non-neuronal components of cholinergic system in the regulation of PBT-cell apoptosis in COPD and demonstrates that Tiotropium regulates CD4+ and CD8+ PBT-cell apoptosis. It provides novel putative pharmacological targets for the resolution of systemic inflammation in COPD.

year	journal	country	edition	language
2011-04-12	Immunobiology

https://doi.org/10.1016/j.imbio.2011.07.013