Effects of cigarette smoke on degranulation and NO production by mast cells and epithelial cells

• Published in: Respiratory research Vol. 6; no. 1; p. 108
• Main Authors: Wei, Xiu M, Kim, Henry S, Kumar, Rakesh K, Heywood, Gavin J, Hunt, John E, McNeil, H Patrick, Thomas, Paul S
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 19-09-2005; BioMed Central; BMC
• Subjects: Animals; Cell Degranulation - drug effects; Cells, Cultured; cigarette smoke; Cysteine; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; epithelial cells; Epithelial Cells - cytology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; mast cells; Mast Cells - drug effects; Mast Cells - metabolism; Mice; Mice, Inbred BALB C; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - metabolism; Nitric Oxide Synthase Type III; Respiratory Mucosa - cytology; Respiratory Mucosa - drug effects; Respiratory Mucosa - metabolism; RNA; Smoking; Tars - pharmacology; Trachea - cytology; Trachea - drug effects; Trachea - metabolism
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/1465-9921-6-108

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.