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F Kuypers

Publications and source records attributed to F Kuypers.

10 recordsLinked to original sources
PubMed1997

Decrease of very late activation antigen-4 and CD36 on reticulocytes in sickle cell patients treated with hydroxyurea.

Sickle cell disease (SCD) is characterized by repeated vaso-occlusive events, which result in substantial morbidity. Abnormal adhesion of sickle red blood cells (RBC) to the vascular endothelium is postulated to play a role in the pathogenesis of vaso-occlusion. Two adhesion receptors, very late activation antigen-4 (VLA-4) and CD36, are found in unusually high numbers on sickle cell reticulocytes and do mediate adhesion of sickle RBC to endothelium. Hydroxyurea (HU) therapy results in fewer vaso-occlusive episodes, and we postulated that HU-related modulation of VLA-4 and CD36 receptors may contribute to its clinical benefit. Using flow cytometry, eight patients were followed from the onset of HU treatment through a mean treatment length of 200 +/- 49 days. Mean corpuscular volume and percent fetal hemoglobin (Hb F) increased from 87% +/- 6% to 98% +/- 9% and 6.6% +/- 3.9% to 12.7% +/- 5.6%, respectively. The percentage of reticulocytes expressing VLA-4 decreased from 29.0% +/- 5.9% to 14.9% +/- 2.3% (P = .0003). Two thirds of the total decrease in VLA-4 expression occurred after 10 weeks of HU and plateaued by 20 weeks. Changes in VLA-4 expression occurred before substantial increases in Hb F. The percentage of reticulocytes expressing CD36 decreased from 55.3% +/- 6.4% to 42.6% (P = .0046). Changes in adhesion receptor expression were not caused by a decrease in reticulocytosis with HU therapy. This report is the first to associate a decrease in adhesion receptor expression with a therapy known to reduce the clinical severity of SCD.

Adolescent↗
PubMed1994

Membrane changes associated with lysis of red blood cells by hypochlorous acid.

This study was carried out to investigate HOCl-induced lysis of human erythrocytes. Using reagent HOCl with isolated red cells, we showed that the rate of lysis was dependent on the dose of HOCl per red cell rather than on the concentration of oxidant. The process was inhibited by scavengers such as methionine and taurine, but only if they were present at the time of addition of HOCl. Lysis was preceded by a decrease in cell density, a change in the deformability of the membrane as evidenced by ektacytometry, and an increase in K(+)-leak. Electron microscopy showed extensive disruption of the membrane. Increasing doses of HOCl caused progressive loss of membrane thiols, but complete thiol oxidation by N-ethylmaleimide did not result in an equivalent rate of lysis. Restoration of oxidised thiols by incubation with glucose did not significantly alter the pattern of lysis. Taken together, these results suggest that thiol oxidation was not responsible for HOCl-mediated lysis. There was evidence of increasing crosslinking of membrane proteins on electrophoresis, only some of which was due to the formation of disulfides. TLC of the membrane lipids indicated that there may be formation of chlorohydrins by reaction of HOCl with the fatty acid double bonds. This reaction results in the formation of a more polar species which, if formed, would be extremely disrupting to the lipid bilayer. The results indicate that HOCl-mediated damage to the membrane proteins or to the lipid bilayer comprises an initial damaging event that sets the cells on a path toward eventual lysis.

Diamide↗
PubMed1993

Iron-dependent free radical generation from the antimalarial agent artemisinin (qinghaosu).

Artemisinin is an important new antimalarial agent containing a bridged endoperoxide. The in vitro antimalarial activity of an artemisinin derivative, arteether, is antagonized by two iron chelators, pyridoxal benzoylhydrazone and 1,2-dimethyl-3-hydroxypyrid-4-one. Similarly, the acute toxicity of artemisinin in mice is antagonized by another chelator, deferoxamine-hydroxyethylstarch. A combination of artemisinin and hemin oxidizes erythrocyte membrane thiols in vitro, and this oxidation is also inhibited by an iron chelator. Thus, iron plays a role in the mechanisms of action and toxicity of artemisinin. The combination of artemisinin and hemin also decreases erythrocyte deformability. Iron probably catalyzes the generation of free radicals from artemisinin since alpha-tocopherol antagonizes the thiol-oxidizing activity of artemisinin and since a spin-trapped free radical signal can be seen by electron paramagnetic resonance only when artemisinin is incubated in the presence of iron.

Animals↗
PubMed1990

Lability of red blood cell membranes to lipid peroxidation: application to humans fed polyunsaturated lipids.

Red blood cell membranes (RBCM) were used to estimate human red blood cell lability to lipid peroxidation in vitro. RBCM were prepared from blood collected from humans fed diets with either 3 or 15% polyunsaturated fatty acids for 80 days. RBCM were isolated by centrifugation, and oxidative stress was induced by in vitro incubation with 0.1 or 0.5 mM tert-butyl hydroperoxide (t-BOOH) in the presence of 0.5 mg added hemoglobin. Lipid Peroxidation was evaluated by measurement of thiobarbituric acid-reactive substances (TBARS). Lipid peroxidation correlated with the protein content of RBCM in both noninduced and t-BOOH-induced lipid peroxidation systems. TBARS production was dependent on the amount of t-BOOH added to the RBCM. The production of TBARS by RBCM incubated with 0.5 mM t-BOOH was correlated with arachidonic acid content in the red blood cells (RBC) from which RBCM were prepared. The methodology developed was useful for comparative estimations of the lability of RBCM to lipid peroxidation.

Adult↗
PubMed1989

Lipid alterations and cellular properties of sickle red cells.

Taken together, our studies and those in other laboratories demonstrate a number of membrane lipid changes in sickle erythrocytes. These include (1) changes in membrane phospholipid dynamics, (2) perturbation of the translocase protein that translocates aminophospholipids from the exterior leaflet to the interior leaflet, (3) perturbation of the interaction between membrane phospholipids and skeletal proteins, and (4) abnormal phospholipid molecular species compositions. The mechanism underlying these alterations may involve several independent effects. Included in these will be the oxidative damage that occurs to these membranes and the dissociation of lipids and proteins that accompanies the sickling process.

Anemia, Sickle Cell↗
PubMed1989

Lipid peroxidation in human red cells.

In this review we have discussed the chemistry and biochemistry of lipid peroxidation as well as lipid repair mechanisms in human RBCs. We have presented findings relating to the effect of lipid peroxidation on the RBC membrane and on several properties that are determinants of RBC survival in vivo. Since we have not discussed how oxidative damage to membrane proteins or hemoglobin may affect RBC survival, the role of lipid oxidation must be considered in a broader perspective. Considerable evidence has recently been reported to indicate that oxidative hemoglobin denaturation plays an extremely important role in RBC survival. Since all cellular components are susceptible to peroxidative damage, it is likely that multiple reactions will be important with regard to RBC oxidant injury, just as they have been implicated in many degenerative processes, and that certain "compartments" of the membrane may be more susceptible than others due to congenital or acquired defects in membrane structure.

Acylation↗
PubMed1984

Rhnull human erythrocytes have an abnormal membrane phospholipid organization.

Rhnull human erythrocytes lack the antigens of the Rhesus blood group system, have an abnormal shape and an increased osmotic fragility, and are associated with mild chronic haemolytic anaemia. Studies with phospholipase A2 and sphingomyelinase C show that the asymmetric distribution of phosphatidylethanolamine (PtdEtn) in the membrane of these cells differs from that found in control cells. The amount of PtdEtn which can be hydrolysed by phospholipase A2 in the presence of sphingomyelinase C in intact Rhnull cells is twice as high as that in normal erythrocytes. In intact Rhnull cells all of the phosphatidylcholine (PtdCho) present in the membrane can be readily exchanged with a PtdCho-specific exchange protein, whereas in control cells 75% is readily exchanged and 25% at a much lower rate. This indicates that PtdCho experiences a relatively fast transbilayer movement in the Rhnull cells. The observation that the loss of two membrane polypeptides in the Rhnull cells leads to abnormal shape, increased osmotic fragility, abnormal PtdEtn distribution and enhanced transbilayer mobility of PtdCho strongly suggests that one or both polypeptides are essential for the maintenance of a proper membrane-membrane skeleton interaction.

Erythrocyte Membrane↗