Inhibition of hypochlorous acid-induced cellular toxicity by nitrite

Chronic inflammation results in increased nitrogen monoxide (⋅NO) formation and the accumulation of nitrite (NO [12pt]{minimal} {amsmath} {wasysym} {amsfonts} {amssymb} {amsbsy} {mathrsfs} {}{-69pt} {document} {equation*}₂⁻{equation*}{document} ). Neutrophils stimulated by various inflammatory mediators release myeloperoxidase to produce the cytotoxic agent hypochlorous acid (HOCl). Exposure of chondrocytic SW1353 cells to HOCl resulted in a concentration- and time-dependent loss in viability, ATP, and glutathione levels. Treatment of cells with NO [12pt]{minimal} {amsmath} {wasysym} {amsfonts} {amssymb} {amsbsy} {mathrsfs} {}{-69pt} {document} {equation*}₂⁻{equation*}{document} but not nitrate (NO [12pt]{minimal} {amsmath} {wasysym} {amsfonts} {amssymb} {amsbsy} {mathrsfs} {}{-69pt} {document} {equation*}₃⁻{equation*}{document} ) substantially decreased HOCl-dependent cellular toxicity even when NO [12pt]{minimal} {amsmath} {wasysym} {amsfonts} {amssymb} {amsbsy} {mathrsfs} {}{-69pt} {document} {equation*}₂⁻{equation*}{document} was added at low (μM) concentrations. In contrast, NO [12pt]{minimal} {amsmath} {wasysym} {amsfonts} {amssymb} {amsbsy} {mathrsfs} {}{-69pt} {document} {equation*}₂⁻{equation*}{document} alone (even at 1 mM concentrations) did not affect cell viability or ATP and glutathione levels. These data suggest that NO [12pt]{minimal} {amsmath} {wasysym} {amsfonts} {amssymb} {amsbsy} {mathrsfs} {}{-69pt} {document} {equation*}₂⁻{equation*}{document} accumulation at chronic inflammatory sites, where both HOCl and ⋅NO are overproduced, may be cytoprotective against damage caused by HOCl. We propose that this is because HOCl is removed by reacting with NO [12pt]{minimal} {amsmath} {wasysym} {amsfonts} {amssymb} {amsbsy} {mathrsfs} {}{-69pt} {document} {equation*}₂⁻{equation*}{document} to give nitryl chloride (NO 2 Cl), which is less damaging in our cell system.