The effect of dialysate on peritoneal phagocyte oxidative metabolism.
The respiratory and oxidative responses of human peritoneal polymorphonuclear leukocytes (PMN) and peritoneal macrophages (PM phi) following exposure to unused continuous ambulatory peritoneal dialysis fluid (CAPD) and early dwell effluent were studied using an open oxygen (O2) electrode system and by measurement of oxygen radical-derived luminol-dependent chemiluminescence. Both cell types responded to stimulation by increasing O2 consumption and by generating chemiluminescence even at external O2 concentrations below 50 microM O2. Oxygen concentrations in the dialysate, as measured by blood gas analysis, were never lower than 118 +/- 8.3 microM O2 even during active peritonitis. Thus oxygen availability does not appear to be rate limiting for phagocyte oxidative metabolism in the peritoneal cavity. Preexposure of both inflammatory cell types to unused fluid or early dwell CAPD effluent significantly reduced both stimulated oxygen uptake and the subsequent ability of these cells to generate chemiluminescence without significantly affecting their viability. Further investigation of this down regulatory phenomenon using unused fluid and laboratory prepared dialysis fluid revealed that low pH (5.3) and high sodium lactate concentration in combination are directly responsible for the suppressive effect of unused fluid and early dwell effluent on cell function. These observations demonstrate that cellular host defense may be impaired early in the dialysis cycle as a result of lactate mediated "stunning" of resident phagocytes. The precise nature of the molecular species responsible for this suppressive effect remains to be identified.
Topley
N
N
Department of Renal Medicine, K.R.U.F. Institute, Royal Infirmary, Cardiff, Wales, United Kingdom.
Alobaidi
H M
HM
Davies
M
M
Coles
G A
GA
Williams
J D
JD
Lloyd
D
D
D015314:Dialysis Solutions / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D008163:Luminescent Measurements; D008165:Luminol / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010529:Peritoneal Cavity / Q000166:cytology; D010538:Peritonitis / Q000378:metabolism; D013203:Staphylococcal Infections / Q000378:metabolism; D013212:Staphylococcus epidermidis
D015314:Dialysis Solutions; D007773:Lactates; D019344:Lactic Acid; D008165:Luminol