Leukotriene Release from Peripheral and Peritoneal Leukocytes Following Exposure to Peritoneal Dialysis Solutions

Abstract

During continuous ambulatory peritoneal dialysis (CAPD), peritoneal host defence mechanisms are repeatedly exposed to dialysis solutions (with unphysiological composition) which may compromise peritoneal immune cell functions. In this context, the current study focused on the capacity of peripheral and peritoneal PMN to release leukotrienes following exposure to conventional CAPD dialysates. PMN were obtained from peripheral blood of healthy volunteers and from the peritoneal effluent of CAPD patients with acute peritonitis. Following isolation, cells were incubated in fresh CAPD dialysates or control buffer, and calcium ionophore A23187-stimulated leukotriene synthesis was measured. Additional experiments included RP-HPLC analysis and radioactivity monitoring of lipoxygenase products in PMN labelled with 14C-arachidonic acid. Leukotriene B4 and leukotrienes C4/D4/E4 were determined by radioimmunoassay. Ionophore-triggered leukotriene release from cells exposed to control buffer was pronounced in inflammatory peritoneal PMN (70.4 +/- 31.3 ng/5 x 10(6) cells LTB4 and 13.4 +/- 19.8 ng/5 x 10(6) cells LTC4/D4/E4, mean +/- SD, n = 14) when compared to healthy peripheral PMN (26.6 +/- 16.9 ng/ml LTB4 and 6.3 +/- 6.6 ng/ml LTC4/D4/E4, n = 12). Incubation in fresh solutions for peritoneal dialysis severely depressed leukotriene release from both cell populations. These results indicate a severe inhibition of cellular responsiveness as a consequence of dialysate exposure which could contribute to the impairment of host defence early in the CAPD cycle.

Peritoneal Dialysis Fluid Inhibition of Polymorphonuclear Leukocyte Respiratory Burst Activation Is Related to the Lowering of Intracellular pH

“…In contrast, the activation of the 5-lipoxygenase pathway resulting in the generation of LTB4 remained unaffected. We have previously demonstrated that leukotriene synthesis by PMN in response to the Ca ionophore (A23187) is inhibited in low-and high-dextrose dialysis fluids [8,13]. The current study appears to contradict these findings but agrees with our previous data using STZ as a stimulus for LTB., gener ation [14], It is likely that the difference in response is related to the different stimuli and that the cells are much more sensitive (in terms of cell function and possibly cytoxicity) to low-pH/lactate-containing fluids in the presence of a pore-forming agonist (A23187) than when responding to a particulate ligand (STZ).…”

“…Although technical improvements in delivery sysAccepted : September 18,1992 terns and better patient training have resulted in a marked reduction in infection rate [1], more attention is now being focused on the biocompatibility of the fluids used in perito neal dialysis. Over the last 10 years, evidence has accumu lated that the dialysis fluids currently used might inhibit host defence mechanisms in the peritoneal cavity [2][3][4][5][6][7][8].…”

Biocompatibility of Peritoneal Dialysis Fluids

“…Polymorphonuclear leukocytes harvested during peritonitis episodes showed> 95% viability following 4 hours i.p. dwell time (9,11).…”

Prolonged preservation of rat peritoneal mesothelial cells (RPMC) and rat peritoneal fibroblasts (RPFB) with neutral pH peritoneal dialysis solution depleted of glucose degradation products (GDPs)

“…In the past two decades, biocompatibility testing for conventional PD solutions has been carried out with various cell types, such as peripheral and peritoneal leukocytes, [11][12][13][41][42][43][44][45][46][47] transformed cell lines, [1][2][3][4]21,22,48 and cells derived from the peritoneum. 6,26,28,[35][36][37][38]42,49 Viability, respiratory burst activity and phagocytic function of polymorphonuclear cells (PMNs), peritoneal macrophages (PMf), and mononuclear cells (MNCs) have been evaluated to assess changes in hostdefense activity caused by PD solutions.…”

“…5,[7][8][9] Exposure of resident peritoneal cells to acidic PD solutions has been shown to have deleterious effects upon the cells, [10][11][12][13] even though, in vivo, the pH is neutralized within 30 to 40 min. 5,[7][8][9] Exposure of resident peritoneal cells to acidic PD solutions has been shown to have deleterious effects upon the cells, [10][11][12][13] even though, in vivo, the pH is neutralized within 30 to 40 min.…”