PERITONEAL-DIALYSIS FLUID INHIBITION OF POLYMORPHONUCLEAR LEUKOCYTE RESPIRATORY BURST ACTIVATION IS RELATED TO THE LOWERING OF INTRACELLULAR PH

In order to elucidate the mechanism of peritoneal dialysis fluid inhib ition of cell functions, laboratory-prepared fluids were used to inves tigate the specific influences of low pH and high lactate concentratio n on neutrophil viability, phagocytosis, respiratory burst activation and leukotriene B4 (LTB4) generation. In the absence of any reduction of viability, respiratory burst activation, stimulated by serum-treate d zymosan (STZ), was significantly inhibited by fluids of low pH conta ining high concentrations of sodium lactate. Neither low pH nor lactat e concentration alone, however, caused significant suppression of this parameter of cell activation. Under the same conditions, the phagocyt osis of STZ was partially inhibited in a lactate- and pH-dependent man ner. In contrast, the generation of LTB4 in response to STZ was unaffe cted by pH and lactate concentration. The incubation of polymorphonucl ear leukocytes (PMN) in fluids containing 35 mM lactate at pH 5.2 resu lted in an immediate and profound lowering in intracellular pH {[pH]i} which was not observed in lactate-containing fluids at neutral pH or at low pH in the absence of lactate. We postulate that the critical lo wering of [pH]i in PMN, caused by the combination of high lactate conc entration and low pH of the dialysis fluids, is responsible for the ob served inhibition of respiratory burst activation. It is also possible that under these conditions, the lactate ion acts as a proton carrier across the cell membrane following the [H+] gradient. The time course of this [pH]i change suggests that host defence mechanisms may be imp aired following short-time exposure to unused dialysis fluid prior to its equilibration in vivo.