HYDROGEN-PEROXIDE GENERATION BY POLYMORPHONUCLEAR LEUKOCYTES EXPOSED TO PERITONEAL-DIALYSIS EFFLUENT

In the presence of peritoneal dialysis effluent (PDE), human polymorph onuclear leukocytes (PMN) showed reduced production of hydrogen peroxi de and hypochlorous acid (H2O2 and HOCl, respectively) when at rest an d when stimulated with both soluble (formylmethionyl-leucyl-phenylalan ine and phorbol myristate acetate) and particulate (Staphylococcus epi dermidis) agonists, This effect occurred in a concentration dependent manner between 0 and 70% (vol/vol) dialysis effluent. The inhibition o f H2O2 and HOCl observed in resting, formy-methionylleucyphenyalanine- stimulated, and S. epidermidis-stimulated PMN was confined to a low-mo lecular-mass (<10,000-Da) fraction of PDE, whereas the inhibition of t he PMA response was equally dispersed throughout both low (<10,000-Da) - and high-molecular-mass (>10,000-Da) fractions, Human serum albumin, a major component of PDE, also inhibited H2O2 and HOCl production by PMN; however, results from cell-free systems suggested that human seru m albumin was not wholly responsible for the inhibition of PMN functio n seen with PDE, The solute(s) responsible did not affect myloperoxida se but very rapidly scavenged H2O2 and HOCl. These data suggest that t he factors capable of affecting H2O2 and HOCl production by PMN accumu late in uremia and are removed from the circulation into dialysis effl uent.