IMPAIRED PHAGOCYTOSIS IN DIALYSIS PATIENTS - STUDIES ON MECHANISMS

Dialysis patients have increased susceptibility to infection and this is, in part, due to impaired phagocytic and bactericidal activities of polymorphonuclear leukocytes (PMNL). The mechanisms responsible for the reduced phagocytosis are not known. Dialysis patients have elevated blood levels of parathyroid hormone (PTH), and available data indicate that PMNL is a target cell for PTH. Chronic exposure to excess PTH may cause accumulation of calcium in PMNL which in turn could adversely affect cellular events leading to their dysfunction. We studied phagocytosis, resting levels of cytosolic calcium ([Ca2+]i), ATP content and the rise in [Ca2+]i in response to ligation of Fc-gamma RIII receptors with 3G8 monoclonal antibody in PMNL from 37 dialysis patients and 48 normal subjects. The PMNL from the dialysis patients displayed impaired phagocytosis, elevated resting levels of [Ca2+]i, decreased ATP content and a smaller rise in [Ca2+]i in response to various doses of 3G8 monoclonal antibody as compared to values obtained in PMNL of normal subjects. Our results suggest that derangements in cellular metabolism and possibly an abnormality in Fc-gamma RIII interaction with antibody and/or the consequences of such interaction are responsible, at least in part, for the impaired phagocytosis of PMNL of dialysis patients. Our data are consistent with the notion that excess PTH may play an important role in the processes leading to impaired phagocytosis.