Angiogenin: A Novel Inhibitor of Neutrophil Lactoferrin Release during Extracorporeal Circulation

Abstract

Degranulation of polymorphonuclear leukocytes (PMNL) occurs during extracorporeal circulation. A degranulation-inhibiting protein identical to angiogenin was recently isolated from high-flux dialyzer ultrafiltrate. This protein inhibits the release of lactoferrin and metalloproteinases from PMNL in vitro. In the present study, we investigated end-stage renal disease patients undergoing regular hemodialysis treatment with either high-flux dialyzers (n = 51) or low-flux dialyzers (n = 44), and chronically uremic patients undergoing hemodiafiltration (n = 30). Hemodialysis therapy with low-flux polysulfone or cellulose triacetate membranes caused no or only minimal reduction (≤8%) of plasma angiogenin levels within 2 h of dialysis treatment associated with a 1.6-fold lactoferrin release from PMNL. Hemodialysis therapy with high-flux membranes (e.g. cellulose triacetate, polymethylmethacrylate) or hemodiafiltration resulted in a reduction of plasma angiogenin levels by 20–40% after 2 h associated with a nearly 4-fold PMNL lactoferrin release. The release of PMNL elastase was not affected by the different treatment modalities used. We conclude that high angiogenin plasma levels protect against lactoferrin release from PMNL during extracorporeal circulation in chronically uremic patients. A decrease of plasma angiogenin between 20 and 40% during extracorporeal circulation, however, results in marked PMNL lactoferrin release. This novel mechanism may explain, at least in part, PMNL degranulation also in non complement activating high-flux membranes.