Erythrocyte lysis by PMA-triggered neutrophil polymorphonuclears: evidence for an hypochlorous acid-dependent process

Human red blood cells (HRBC) were efficiently lysed when incubated with neutrophil polymorphonuclears (PMN) in the presence of phorbol-myristate-acetate (PMA), as detected by a 4-hr 51Cr release assay. The lysis was virtually absent in the presence of catalase, azide or cyanide and in the absence of chloride ions. These findings indicate the involvement of the myeloperoxidase (MPO)-hydrogen peroxide (H2O2)-chloride (Cl-) system in the cytolytic process. As the MPO-H2O2-Cl- system is capable of generating the powerful oxidant hypochlorous acid (HOCl), cytotoxicity assays were performed in the presence of taurine, glycine, serine and valine to scavenge this potentially lytic agent. Each of these compounds efficiently inhibited the HRBC lysis by PMA-triggered PMN, as well as the lysis caused by HOCl in a cell-free system. Thus, the results suggest that HOCl, or an agent with similar reactivity, plays a key role in the PMA-dependent PMN-mediated cytotoxicity against HRBC targets.