Impaired cellular host defence in peritoneal dialysis by two granulocyte inhibitory proteins

Abstract

Bacterial and fungal peritonitis is associated with a high risk of morbidity and mortality in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Impaired cellular host defence in the peritoneal cavity underlies this risk. Two granulocyte inhibitory proteins with a molecular weight of 28,000 dalton (GIP I) and about 9500 dalton (GIP II) with homology to light-chain proteins and beta 2-microglobulin, respectively, were isolated from peritoneal dialysis effluents. In vitro, both granulocyte inhibitory proteins inhibit PMNL glucose uptake, phagocytosis and intracellular killing of bacteria. The IC50 of GIP I or GIP II required for inhibition of half-maximal FMLP-induced or PMA-stimulated PMNL function was found to be in the nanomolar range, suggesting very specific inhibition. These data may explain, at least in part, defective local cellular host defence in CAPD patients.