title: Retracted: In vitro anticholinergic drugs affect CD8+ peripheral blood T-cells apoptosis in COPD.
abstract: 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.
authors.affiliation: Institute of Biomedicine and Molecular Immunology A. Monroy (IBIM), Italian National Research Council (CNR), Palermo, Italy. profita@ibim.cnr.it
authors.forename: Mirella
authors.initials: M
authors.lastname: Profita
authors.forename: Loredana
authors.initials: L
authors.lastname: Riccobono
authors.forename: Angela Marina
authors.initials: AM
authors.lastname: Montalbano
authors.forename: Anna
authors.initials: A
authors.lastname: Bonanno
authors.forename: Maria
authors.initials: M
authors.lastname: Ferraro
authors.forename: Giusy Daniela
authors.initials: GD
authors.lastname: Albano
authors.forename: Stefania
authors.initials: S
authors.lastname: Gerbino
authors.forename: Paola
authors.initials: P
authors.lastname: Casarosa
authors.forename: Michael Paul
authors.initials: MP
authors.lastname: Pieper
authors.forename: Mark
authors.initials: M
authors.lastname: Gjomarkaj
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002794:Choline / Q000097:blood; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018680:Cholinergic Antagonists / Q000378:metabolism / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism; D043587:Receptor, Muscarinic M3 / Q000378:metabolism; D012602:Scopolamine Derivatives / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D000069447:Tiotropium Bromide
chemical_list: D018680:Cholinergic Antagonists; D016328:NF-kappa B; D043587:Receptor, Muscarinic M3; D012602:Scopolamine Derivatives; D002795:Choline O-Acetyltransferase; D053148:Caspase 3; D053181:Caspase 8; D002794:Choline; D000069447:Tiotropium Bromide