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.
Highlights
Cigarette smoke is a complex medium containing approximately 4000 different constituents [1] separated into gaseous and particulate phases
Effect of cigarette smoke solution (CSS) on degranulation and [NOX] generation by RBL-2H3 RBL-2H3 cells activated with either IgE/DNP or A23187 showed a concentration-dependent decrease in degranulation after incubation with CSS (0.125%–1.0%) for 6 h (Fig 1, p < 0.0001, ANOVA)
Effect of nicotine on degranulation and [NOX] in RBL2H3, A549, NHTBE, and airway epithelial cells (AEC) In order to investigate whether nicotine, the major component of cigarette smoking in particulate phase, is responsible for the inhibition of degranulation and production of nitric oxide, RBL-2H3 cells were incubated in nicotine solutions (62.5–250 μM) adjusted to physiological pH for 24 h
Summary
Cigarette smoke is a complex medium containing approximately 4000 different constituents [1] separated into gaseous and particulate phases. Pulmonary effects of cigarette smoke include chronic obstructive pulmonary disease, increased airway reactivity, exacerbations of asthma, and an increased frequency of pulmonary infections. These effects are considered to be due to the direct actions of cigarette-derived toxins and ciliotoxins causing connective tissue destruction, hypersecretion, pooling of mucus and blebbing of membranes of endothelial cells. Cigarette smoke reduces levels of exhaled nitric oxide in active and passive smokers, suggesting that it inhibits NO production [3,4,5]. Su et al [6] have shown that exposure to cigarette smoke extract inhibits the activity, protein and messenger RNA of NO synthase (eNOS) in pulmonary artery endothelial (page number not for citation purposes)
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