Enhancement of Reactive Oxygen Species Production and Chlamydial Infection by the Mitochondrial Nod-like Family Member NLRX1 (original) (raw)
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Influence of polysulfone and hemophan hemodialysis membranes on phagocytes
General Physiology and Biophysics
The aim of the study was to compare the effect of hemophane and polysulfone membranes on the phagocyte-derived production of reactive oxygen species (ROS) as well as on neutrophil CD11b and CD62L expression in patients undergoing regular hemodialysis. The effects of hemodialysis membranes were also studied in in vitro conditions after coincubating them with differentiated HL-60 cells. ROS production was measured using chemiluminometric and flow cytometric methods. Expression of CD11b, CD62L and mitochondrial membrane potential were detected by monoclonal antibodies and by the JC-1 fluorescent probe, respectively. Depressed ROS production was observed in patients already before dialysis. Further decrease in ROS production and an increase in CD11b expression were observed especially in patients after hemophan hemodialysis. Decreased ROS production and increased CD11b expression were observed also after incubation of HL-60 cells with hemophan membranes. Mitochondrial membrane potential dropped only after incubating cells with hemophan membranes proving its more serious adverse effects in comparison with the polysulfone membrane. In conclusion, deleterious effects of hemodialysis on the metabolic activity of phagocytes were proved. Combining chemiluminescent and flow cytometric methods for the detection of ROS production and determining mitochondrial membrane potential can be useful tools for the analysis of material biocompatibility. opsonized in human serum; MRF, median of relative fluorescence.
Clinical & Experimental Immunology, 2008
Production of reactive oxygen intermediates (ROI) by neutrophils (PMN) in vivo was examined by a whole blood assay using dichlorofluorescein-diacetate (DCFH-DA) in 10 patients each dialysed consecutively with two different dialyser membranes. Haemodialysis (HD) with cuprophan membrane (CM) led to a significantly (P < 0.001) more pronounced ROI production by PMN (2.4 +/- 0.5-fold increase in intracellular oxidation of DCFH-DA) compared with HD with polysulfone membranes (PM; 1.5 +/- 0.2-fold). HD with CM induced a decrease in PMN count by about 90%, whereas PM induced a decrease by only 25% (P < 0.001). In CM patients maximal ROI production coincided with the nadir in PMN count. All patients dialysed with CM showed a clear increase in serum levels of Bb fragments, whereas PM-dialysed patients did not. In this respect, however, no clear time relationship was seen to the kinetics of ROI production, nor to the disappearance of neutrophils from the circulation. Evaluating a direct effect of the dialysis membranes on PMN demonstrated that incubation of neutrophils with hollow fibres of the CM but not of the PM in the absence of plasma induces significant ROI production by PMN. Our study thus indicates that ROI production by PMN during HD correlates to membrane biocompatibility. Furthermore, one might speculate that also independently from but perhaps in addition to complement activation, reactive oxygen products are critically involved in the generation of haemodialysis-associated neutrophil emigration.
Influence of Different Hemodialysis Membranes on Red Blood Cell Susceptibility to Oxidative Stress
Artificial Organs, 2000
Oxidative stress is crucial in red blood cell (RBC) damage induced by activated neutrophils in in vitro experiments. The aim of the study was to evaluate whether the bioincompatibility phenomena occurring during hemodialysis (HD) (where neutrophil activation with increased free radical production is well documented) may have detrimental effects on RBC. We evaluated RBC susceptibility to oxidative stress before and after HD in 15 patients using Cuprophan, cellulose triacetate, and polysulfone membrane. RBC were incubated with t-butyl hydroperoxide as an oxidizing agent both in the presence and in the absence of the catalase inhibitor sodium azide. The level of malonaldehyde (MDA), a product of lipid peroxidation, was measured at 0, 5, 10, 15, and 30 min of incubation. When Cuprophan membrane was used, the MDA production was significantly higher after HD, indicating an increased susceptibility to oxidative stress in comparison to pre-HD.
Nephrology Dialysis Transplantation, 2006
Background. There is increased oxidative stress in patients undergoing haemodialysis (HD); however, little is known of how different dialysis membranes contribute to the oxidative stress induced by the dialysis procedure per se. We therefore studied the influence of two different dialysis membranes on oxidative stress during HD. Methods. Eight patients undergoing HD three times per week were enrolled in this cross-controlled study. Patients sequentially received HD using polysulphone (PS) and regenerated cellulose (RC) dialysis membranes for 1 week each. Blood samples were collected in the last section of each hollow fibre 0, 15, 120 and 240 min after starting HD. We determined superoxide anion production derived from neutrophils, superoxide dismutase (SOD) and glutathione peroxidase (GPx) derived from washed red cells, plasma myeloperoxidase (MPO), plasma thiobarbituric acid-reactive substances (TBARS), plasma advanced oxidation protein products (AOPP) and serum 8-hydroxy-2 0deoxyguanosine (8-OHdG). Results. Leukocyte numbers, including neutrophils, lymphocytes and monocytes, decreased significantly after 15 min of dialysis, more so with RC than with PS membrane. For both membranes, superoxide anion production transiently increased during the first 15 min whereas the post-dialysis production was decreased. Plasma MPO levels persistently increased during dialysis with the two membranes. Moreover, the increase was more marked with RC than with PS membrane. AOPP and 8-OHdG levels increased progressively when using RC membranes. There were no significant differences in SOD, GPx, TBARS, AOPP and 8-OHdG levels between the two membranes.
Background. Among patients with defects of the phagocytic component of the immune system, chronic haemodialysis patients are highly susceptible to microbial infections characterized by high morbidity/ mortality, related to an impairment of the phagocytic response. Therefore the potential influence of dialysis membrane biocompatibility on the activity of polymorphonuclear (PMN) granulocytes from dialysis patients was investigated in this study. Methods. Nineteen patients in haemodialysis were included in the protocol and divided into two groups: a control group (7 patients) and a study group (12 patients). The study group patients were treated for subsequent periods of 1 month with different dialysis membranes: low flux excebrane E membrane (CL-E), low flux polysulfone (PS). The control group patients were treated with a low flux modified cellulose membrane (SMC) for the entire observation period. The aetiology of end-stage renal disease included glomerulonephritis, nephroangiosclerosis and interstitial nephropathy. Following each period of treatment, clinical and haematological parameters were evaluated; phagocytosis and microbicidal activity of PMNs from uraemic patients against Klebsiella pneumoniae, the pathogen which can pose severe problems in immune depressed patients, were investigated in parallel. Results. The data evidence that both clinical and haematological parameters remained unchanged during the study period and no differences were found among treatments. On the contrary, the PMN activity varied according to the type of the membrane. In fact, the use of both PS and CL-E, in contrast to SMC, resulted in a PMN functionality similar to that observed in healthy subjects. Conclusions. These results provide evidence that the depressed PMN activities in dialysis patients may be influenced by membrane biocompatibility in such a way to be totally restored.
Oxidative Stress Potentials of Different Synthetic Hemodialysis Membranes
Dialysis & Transplantation, 2008
BACKGROUND: Oxidative stress resulting from membranes is dependent on the increase in production of toxic-free oxygen radicals occurring through the mediation of complement and leukocyte activation. Increased oxidative stress causes morbid results such as erythropoietin resistance, accelerated aging, and atherosclerosis. This study aimed to determine the stress potentials of 2 distinct synthetic membranes different than used in previous studies. In our study, the effects of using polysulfone (PSU) and ethylene vinyl alcohol (EVAL) for 3-month periods in the same patient group on malondialdehyde (MDA) levels, biomarker for oxidative stress, and proinfl ammatory cytokine production were compared.
The International Journal of Artificial Organs, 1987
Polymethylmethacrylate (PMMA) membranes with different net electric charges and percentage water contents (anionic 71%, neutral 70%, cationic 75%) were evaluated for their ability to stimulate plasma-free human polymorphonuclear neutrophils (PMN), and compared for potency to cuprophan (Cu), already described as being a potent trigger of PMN. The release of lysozyme, β-glucuronidase, lactic dehydrogenase (LDH), and the generation of a platelet aggregating activity were studied in the supernatants from plasma-free human PMN incubated with different membranes. The PMN intracellular content of neutrophil cationic proteins (NCP), elastase, and cathepsin G were also studied by immunofluorescence using specific antisera on smears of PMN before and after incubation with each membrane.Only cationic, but not anionic or neutral PMMA induced a marked release of lysozyme (range 20-25% of the sonicated control, assumed as 100%), and β-glu-coronidase (40-43%), and marked depletion of the intracell...
Artificial Organs, 2007
In an in vivo crossover trial, we compared a cellulosic with a synthetic dialyzer with respect to polymorphonuclear cells (PMN) function and apoptosis, cytokine serum levels and synthesis by peripheral blood mononuclear cells (PBMC), and complement activation. Twenty hemodialysis (HD) patients were assigned in alternate order to HD with cellulose acetate (CA) or polysulfone (PS) dialyzer. After 2 weeks, patients were crossed over to the second dialyzer and treated for another 2 weeks. Apoptosis was assessed by flow cytometry in freshly isolated PMN. Phagocytosis and production of peroxide by PMN were studied by flow cytometry in whole blood. PBMC were isolated from blood samples and incubated for 24 h with or without lipopolysaccharide (LPS). There was no impact of dialyzer biocompatibility on PMN apoptosis and function, cytokine synthesis by PBMC or on their serum levels, serum levels of C3a, and terminal complement complex (TCC). Nevertheless, after HD, serum levels of complement correlated negatively with PMN phagocytosis and peroxide production, and positively with PMN apoptosis and cytokine production by PBMC.