Are granulocyte inhibitory proteins contributing to enhanced susceptibility to infections in uraemia?
Infectious complications are still a major cause of morbidity and mortality in patients undergoing regular dialysis treatment. This increased morbidity and mortality of patients with uraemia has been attributed to the dysfunction of polymorphonuclear leukocytes (PMNLs). Uraemia contributes to impaired PMNL function by means of disarrangements in cellular biochemistry and biology. Reduced chemotaxis, adherence, oxidative activity, and glucose consumption in response to phagocytic challenge have been reported. Several compounds present in uraemic serum have been isolated and characterized to inhibit the biological activity of PMNLs. A first granulocyte inhibitory protein (GIP I) responsible for the PMNL dysfunction in uraemia has been isolated and characterized. The polypeptide, with a molecular weight of 28 000 Da, inhibits the uptake of deoxyglucose, chemotaxis, oxidative metabolism, and intracellular bacterial killing by PMNLs. A second granulocyte inhibitory protein (GIP II), with a molecular weight of 9500 Da, has been isolated from plasma ultrafiltrates obtained from haemodialysis patients. It interferes with similar functions of PMNLs. GIP I displays homology with light chain protein and GIP II with beta 2-microglobulin, respectively. Both proteins were also isolated from peritoneal dialysis effluents. Isolated kappa and lambda light chain monomers and dimers from haemodialysis and peritoneal dialysis patients also inhibit several PMNL functions. Recently, a PMNL degranulation inhibiting protein (DIP) was purified from plasma ultrafiltrates obtained from patients undergoing regular haemodialysis therapy. DIP shows homology with angiogenin and inhibits spontaneous as well as stimulated PMNL degranulation. These proteins may explain at least in part the enhanced susceptibility to infections in haemodialysis and peritoneal dialysis patients.
Haag-Weber
M
M
Department of Medicine, University of Vienna, Austria.
Hörl
W H
WH
D016207:Cytokines / Q000502:physiology*; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000502:physiology; D007239:Infections / Q000209:etiology*; D009504:Neutrophils / Q000502:physiology*; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects; D014511:Uremia / Q000276:immunology*
D016207:Cytokines; D007147:Immunoglobulin Light Chains; C085114:granulocyte inhibitory protein, human