Hypochlorite-induced damage to red blood cells: evidence for the formation of nitrogen-centred radicals

Abstract

Activation of phagocyte cells both in vivo and in vitroresults in the generation of O₂^-• and H₂O₂ and the release of the enzyme myeloperoxidase.¹ Hypochlorite (HOCl) is formed by the myeloperoxidase-catalysed reaction of H₂O₂ with Cl^- ions.² HOCl is important in bacterial cell killing,³ but excessive or misplaced generation of HOCl can cause tissue damage; this is believed to be important in a number of diseases including atherosclerosis, rheumatoid arthritis and some cancers.^4–6 Exposure of red blood cells to HOCl is known to result in cell lysis. The rate of cell lysis has been shown to be dependent on the dose of HOCl per cell.⁷ Treatment of red blood cells with HOCl is known to result in the rapid depletion of intracellular glutathione, which precedes haemoglobin oxidation, formation of chloramines or the oxidation of membrane thiol groups.^7,8 However, the mechanism of HOCl-mediated cell lysis is still not well understood. Radicals have not been previously implicated as intermediates in HOCl-mediated cell lysis, but evidence has recently been presented for the involvement of radicals in HOCl-mediated oxidation of plasma proteins (Eq. 1).^9–11