IMPAIRED CELLULAR HOST-DEFENSE IN PERITONEAL-DIALYSIS BY 2 GRANULOCYTE INHIBITORY PROTEINS

Bacterial and fungal peritonitis is associated with a high risk of mor bidity and mortality in patients undergoing continuous ambulatory peri toneal dialysis (CAPD). Impaired cellular host defence in the peritone al cavity underlies this risk. Two granulocyte inhibitory proteins wit h a molecular weight of 28 000 dalton (GIP I) and about 9500 dalton (G IP Il) with homology to light-chain proteins and beta(2)-microglobulin , respectively, were isolated from peritoneal dialysis effluents. In v itro, 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 PM A-stimulated PMNL function was found to be in the nanomolar range, sug gesting very specific inhibition. These data may explain, at least in part, defective local cellular host defence in CAPD patients.