Intracellular acidification mediates the inhibitory effect of peritoneal dialysate on peritoneal macrophages Academic Article uri icon

abstract

  • Commercial peritoneal dialysis solution (CDS) is known to have a detrimental effect on the capacity of peritoneal macrophages (PM�) to kill bacteria and produce acute phase cyfokines. This cytotoxic effect is largely caused by the low pH of CDS. Because the cytoplasmic pH (pHi) is an important determinant of cellular function, the effect of CDS on the pHi of PM� from continuous ambulatory peritoneal dialysis pa- tients was studied. The pHi of PMwas measured fluorometrically in N-hydroxyethylpiperazine-N'-2-eth- anesulfonic acid (HEPES)-buffered salt solution (HBSS) or CDS at pH values of 5.3, 6.5, and 7.0, values that representthe pH existing in dialysate during the first 30 mm of dwell time. For any given pH ofthe experimen- tal medium, the pHi was always more acidic in CDS than in HBSS. When PMP were incubated with a lactate-containing HBSS, a cellular acidification was observed that was similar to that attained by expo- sure to CDS at the same pH. This supports the hypoth- esis that the decrease in pHi was due to the influx of lactic acid from the CDS into the PM�. In order to demonstrate a causal association between the CDS- induced cellular acidification and a defect in phago- cytosis and cytokine production, these functions were studied after pHi clamping by means of K�/nigericin. It was found that clamping pHi to values below 6.5 led to a markedly reduced tumor necrosis factor-a pro- duction and phagocytosis. However, at values of pHi >6.5, these functions were normal. The acid loading of PMwith CDS was followed by a partial recovery of pHi toward the resting pHi. This recovery reflects the activity of the Na�/Hexchanger, as evidenced by its sensitivity to amiloride and an H�-ATPase sensitive to

publication date

  • January 1, 1995