ISOLATION OF A GRANULOCYTE INHIBITORY PROTEIN FROM UREMIC PATIENTS WITH HOMOLOGY OF BETA(2)-MICROGLOBULIN

Increased incidence of infection in uraemic patients is mainly caused by granulocyte dysfunction. Recently we discovered a granulocyte inhib itory protein (GIP I) in the ultrafiltrate of haemodialysis patients, that inhibits four fundamental functions of polymorphonuclear leukocyt es (PMNLs). We now report on the isolation of a further polypeptide in end-stage renal disease patient ultrafiltrate using a polyamide filte r with biological activity inhibiting healthy PMNL function in vitro. This protein (GIP II) has a molecular weight of about 9500 Da. In-vitr o nanomolar concentrations inhibit PMNL O2- production and glucose upt ake stimulated by phorbol-myristate-acetate (PMA), but not by formyl-m ethionyl-leucyl-phenylalanine (FMLP). In-vitro studies were performed to compare the effects of GIP I and GIP II on several PMNL functions. In contrast to GIP II, GIP I inhibits only FMLP-, but not PMA-stimulat ed PMNL glucose uptake. The NH2 terminal amino acid sequence (21 amino acids) of GIP II shows homology to beta2-microglobulin. Commercially available intact beta2-microglobulin had no effect on PMNL glucose upt ake and O2- production. The beta2-microglobulin homologue protein isol ated from plasma ultrafiltrates of uraemic patients cross-reacts with three different commercially available assays for intact beta2-microgl obulin. Therefore, beta2-microglobulin levels measured in the plasma u ltrafiltrates of regular haemodialysis patients are overestimated with contribution of an uncertain amount of the beta2-microglobulin homolo gue protein (GIP II).