Nephrol Dial Transplant (1994) 9: 382-388
© 1994 European Renal Association-European Dialysis and Transplant Association
research-article
Isolation of a granulocyte inhibitory protein from uraemic patients with homology of ß2-microglobulin
Division of Nephrology, Department of Medicine, University of Vienna Austria
Correspondence and offprint requests to: Correspondence and offprint requests to: Prof. Dr. Dr. W. H. Hörl, Med. Univ. Kiinik UI, Wahringer Gurtel 18-20, A-1090 Wien
Increased incidence of infection in uraemic patients is mainly caused by granulocyte dysfunction. Recently we discovered a granulocyte inhibitory protein (GIP I) in the ultrafiltrate of haemodialysis patients, that inhibits four fundamental functions of polymorphonuclear leukocytes (PMNLs). We now report on the isolation of a further polypeptide in end- stage renal disease patient ultrafiltrate using a polyamide filter with biological activity inhibiting healthy PMNL function in vitro.
This protein (GIP II) has a molecular weight of about 9500 Da. In-vitro nanomolar concentrations inhibit PMNL 02 production and glucose uptake stimulated by phorbol-myristate-acetate (PMA), but not by formyl-methionyl-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-stimulated PMNL glucose uptake. The NH2 terminal amino acid sequence (21 amino acids) of GIP II shows homology to ß-microglobulin. Commercially available intact ß-microglobulin had no effect on PMNL glucose uptake and 02 production. The ß-microglobulin homologue protein isolated from plasma ultrafiltrates of uraemic patients cross-reacts with three different commercially available assays for intact ß-microglobulin. Therefore, ß-microglobulin levels measured in the plasma ultraffitrates of regular haemodialysis patients are overestimated with contribution of an uncertain amount of the ß-microglobulin homologue protein (GIP II).
Keywords: beta2-microglobulin; glucose uptake; granulocyte dysfunction; haemodialysis; neutrophil; oxidative burs
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