On the kinetics of complement activation, leucopenia and granulocyte-elastase release induced by haemodialysis

Abstract

In order to elucidate the kinetics of haemodialysis-induced activation of complement, leucopenia and release of granulocyte-elastase, 10 patients (three females and seven males; mean age 47.8 years) were extensively studied during a 4 h haemodialysis treatment and for the following 24 h, and further compared with a healthy control group. Prior to dialysis patients had normal leucocyte count, plasma elastase bound to alpha 1-proteinase inhibitor (E-alpha 1P1) and total haemolytic complement, whereas plasma C3d was higher and plasma C5a lower than in controls. Haemodialysis induced initial leucopenia and subsequent rebound phenomenon lasting 24 h post treatment. These alterations were due to almost selective changes in neutrophile count as monocyte and lymphocyte counts, apart from decrease in the first 30 min, were unchanged. Total haemolytic complement decreased initially during dialysis and rose at the end. Generation of C5a within the dialyser was evident by demonstration of high levels of this anaphylatoxin in dialyser effluent plasma; maximal values observed coincided with the nadir of leukopenia. Plasma C3d and E-alpha 1P1 both progressively rose during dialysis. After termination of extracorporeal circulation the disappearance rates (T/2) were approximately 6 h and 2.5 h respectively. Haemodialysis thus induces changes in the complement and leucocyte system resembling an acute inflammation, which out-lasts the treatment period.

Quantum Proteolytic Activation of Chemokine CCL15 by Neutrophil Granulocytes Modulates Mononuclear Cell Adhesiveness

“…Calcium mobilization assays with monocytes, CCR1-transfected CHO-K1 cells, and THP-1 cells displayed a remarkable increase in agonistic potency of the N-terminal truncated CCL15 (24 -92) or CCL15 compared to full-length CCL15. For monocytes, EC 50 values for full-length CCL15 are above 1 M and decrease below 1 nM for CCL15 (24 -92) and CCL15 . Chemotaxis assays with the different CCL15 molecules on monocytes do not show such a remarkable difference of their chemotactic potency.…”

“…Processing of CCL15 was induced in two different models: 1) by incubation of CCL15 with isolated PMNs and 2) by hemofiltration of blood from renal insufficiency patients, a treatment in which substantial activation of PMNs and monocytes by interaction with the filter membrane has been described previously (49,50). Proteolytic processing of plasma CCL15 during hemofiltration is suggested by different compositions of CCL15-IR material in plasma and HF of CRF patients.…”

On the Biocompatibility of IBM 2997 Continuous Flow Plateletapheresis

“…In contrast to filtration cytapheresis, complement activation is unlikely to occur during centrifugation cytapheresis (11). Complement acitvation is characteristically accompanied by increased chemiluminescence activity by stimulated cells (5,10) and clinical symptoms of pulmonary sequestration of leukocytes (9). In conclusion, our results for granulocyte-related cellular and humoral parameters provide no significant evidence of cytapheresis-mediated activation or release reactions of clinical consequence.…”

Efficacy and Safety of a Polyester Leukocyte Removal Filter for Whole Blood and Red Cell Concentrate Filtration

“…Frequently observed adverse clinical reactions to other models of extracorporeal blood circuits, such äs haemodialysis and cardiopulmonary bypass, have been ascribed to granulocyte activation with the concomitant generation of large amounts of toxic oxygen species (e. g. Superoxide anion, hydrogen peroxide), discharge of primary and secondary granule contents (e. g. elastase, cathepsin) and complement activation (7)(8)(9)(10)(11)(12).…”