Phagocytic killing of microorganisms by radical processes: consequences of the reaction of hydroxyl radicals with chloride yielding chlorine atoms.

ABSTRACT

Chloride anions and hydrogen peroxide serve as substrates for myeloperoxidase (MPO) in order to produce hypochlorous acid (HOCl) as one of the major killing agents of phagocytic leukocytes. Apart from this role of being a substrate for the MPO-reaction the chloride anion has been considered as unreactive and has not been implicated in radical reactions which contribute to the killing process. From the inherent reactivities of the pertinent radicals (as determined by pulse radiolysis experiments), the great abundance of chloride, and the most probable distribution of reactants within the phagosome, we deduce estimates for the average life-time and free diffusion path-length in this milieu and arrive at a model according to which chloride ions enter into radical chains and influence the killing of ingested bacteria to an extraordinarily high extent. We propose that hydroxyl radicals--despite some controversial arguments in the literature--may still be considered as important contributors to cell killing especially since we show that their reactions are made more effective by producing chlorine radicals in a cyclic process. We furthermore present arguments how the phagocyte may protect itself from harmful actions of HOCl and H2O2 after the superoxide-generating activity of NADPH oxidase is turned off.