title: Cigarette smoke extract modulates respiratory defence mechanisms through effects on T-cells and airway epithelial cells.
abstract: Chronic obstructive pulmonary disease (COPD) is a disease primarily caused by cigarette smoking, which in turn has been shown to affect the susceptibility to and progression of airway infections. The question addressed in this study was how components from cigarette smoke could affect the defence mechanisms of T-cells and epithelial cells, and thereby contribute to the development of the COPD pathology. T-cells and monocytes were isolated from buffycoats from healthy donors and T-cell responses studied in response to cigarette smoke extract (CSE). Activation level (CD25 expression), proliferation (BrdU incorporation) and intracellular expression of the cytotoxic markers granzyme-b and TIA-1 were determined using flowcytometry. Normal human bronchial epithelial cells were obtained from Cambrex and differentiated in air-liquid interface cultures. After exposure to CSE barrier function (trans-epithelial electric resistance, TEER), MUC5AC and interleukin-8 production were measured. T-cell activation, proliferation and expression of the cytotoxic proteins granzyme-b and TIA-1 were significantly reduced in response to 0.5-1% of CSE. The epithelial cells were more resistant to CSE and responded at doses 20 times higher than T-cells. The expression of interleukin-8 and MUC5AC was significantly increased after exposure to 15% and 30% CSE and TEER was largely unaffected at 30% CSE but clearly reduced at 40% CSE. This study shows that mechanisms, in both T-cells and airway epithelial cells, involved in the defence against infectious agents are modulated by CSE.
authors.affiliation: Department of Respiratory Medicine and Allergology, Lund University Hospital, 221 85 Lund, Sweden. Pernilla.Glader@med.lu.se
authors.forename: Pernilla
authors.initials: P
authors.lastname: Glader
authors.forename: Sebastian
authors.initials: S
authors.lastname: Möller
authors.forename: Johanna
authors.initials: J
authors.lastname: Lilja
authors.forename: Elisabet
authors.initials: E
authors.lastname: Wieslander
authors.forename: Claes-Göran
authors.initials: CG
authors.lastname: Löfdahl
authors.forename: Karin
authors.initials: K
authors.lastname: von Wachenfeldt
mesh_terms: D001980:Bronchi / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012906:Smoke; D012907:Smoking / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D014026:Nicotiana
chemical_list: D016209:Interleukin-8; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D012906:Smoke