title: Effects of cigarette smoke on degranulation and NO production by mast cells and epithelial cells.
abstract: Exhaled nitric oxide (eNO) is decreased by cigarette smoking. The hypothesis that oxides of nitrogen (NOX) in cigarette smoke solution (CSS) may exert a negative feedback mechanism upon NO release from epithelial (AEC, A549, and NHTBE) and basophilic cells (RBL-2H3) was tested in vitro. CSS inhibited both NO production and degranulation (measured as release of beta-hexosaminidase) in a dose-dependent manner from RBL-2H3 cells. Inhibition of NO production by CSS in AEC, A549, and NHTBE cells was also dose-dependent. In addition, CSS decreased expression of NOS mRNA and protein expression. The addition of NO inhibitors and scavengers did not, however, reverse the effects of CSS, nor did a NO donor (SNP) or nicotine mimic CSS. N-acetyl-cysteine, partially reversed the inhibition of beta-hexosaminidase release suggesting CSS may act via oxidative free radicals. Thus, some of the inhibitory effects of CSS appear to be via oxidative free radicals rather than a NOX-related negative feedback.
authors.affiliation: School of Pathology, Faculty of Medicine, UNSW, Sydney, Australia. wxm1974@hotmail.com
authors.forename: Xiu M
authors.initials: XM
authors.lastname: Wei
authors.forename: Henry S
authors.initials: HS
authors.lastname: Kim
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Kumar
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Heywood
authors.forename: John E
authors.initials: JE
authors.lastname: Hunt
authors.forename: H Patrick
authors.initials: HP
authors.lastname: McNeil
authors.forename: Paul S
authors.initials: PS
authors.lastname: Thomas
mesh_terms: D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013638:Tars / Q000494:pharmacology*; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D013638:Tars; C024746:tobacco tar; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse