Effects of cigarette smoke on degranulation and NO production by mast cells and epithelial cells.
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.
Wei
Xiu M
XM
School of Pathology, Faculty of Medicine, UNSW, Sydney, Australia. wxm1974@hotmail.com
Kim
Henry S
HS
Kumar
Rakesh K
RK
Heywood
Gavin J
GJ
Hunt
John E
JE
McNeil
H Patrick
HP
Thomas
Paul S
PS
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*
D013638:Tars; C024746:tobacco tar; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse