Erythrocytes sickle

Finch, J.T., et al. Stmcture of sickled erythrocytes and of sickle-cell hemoglobin fibers. Proc. Natl. Acad. Sci. USA 70 718-722, 1973. 

Sickle erythrocytes have increased surface expression of CD36. Microvascular endothelial cells do express CD36. Adhesion between these CD36 molecules of the two cells types can be mediated via the bridging ligand thrombospondin". Indeed plasma thrombospondin levels are increased in SCA patients with pain crisis [15]. 

Although HU may mediate some of its clinical benefits through its positive effect on HbF expression, these data also suggest that it may, by a yet-to-be defined mechanism of action, modulate the clinical severity of SCA. One possible pathway is that among the two incriminated interacting cell partners (sickle erythrocyte and endothelial cell) involved in vaso-adhesion and occlusion, HU may also affect the phenotype status of endothelial cells so that its adhesogenic (structural) and/or vasoregulatory (functional) properties are modified in a favorable manner. 

Elevated ET-1 in SCA patients, even in the steady state, may play an important role in the dehydration of sickle erythrocytes and the resulting enhanced intra-erythrocytic HbS polymerization. Indeed, it has been shown that ET-1 activates Ca2+- gated K+ channels in mouse erythrocytes [34]. ET-1, as a pro-inflammatory agonist, has been shown to induce the production of inflammatory cytokines by monocytes. One of the cytokines, namely TNFa enhances the adherence of sickle erythrocytes to vascular endothelium [35]. In addition, endothehns upregulate the expression of endothelial adhesion molecules such as ICAM-l, VCAM-1 and E-se-lectin, which participate in the recruitment of white cells to the site of inflammation. The overall conclusions that can be drawn from these data is that ET-1 plays a critical role in the vasospasm and inflammation that result in VOC. The major effect of HU in ameliorating the clinical symptoms of SCA likely results from its ability to inhibit the chronically activated ET-1 expression in SCA patients. 

Hebbel R. Adhesive interactions of sickle erythrocytes with endothelium. J Clin Invest 1997 100 S83-86. 

Wick T, Kaye N, Jensen W. Unusually large von Willebrand factor multimers increase adhesion of sickle erythrocytes to human endothelial cells under controlled flow. N Engl J Med 1982 337 1584-1590. 

Shiu YT, Udden MM, McIntire LV. Perfusion with sickle erythrocytes up-reg-ulates ICAM-1 and VCAM-1 gene expression in cultured human endothelial cells. Blood 2000 95 3232-3241. 

Phelan M, Perrine SP, Brauer M, Faller DV. Sickle erythrocytes, after sickling, regulate the expression of the en-dothelin-1 gene and protein in human endothelial cells in culture. J Clin Invest 1995 96 1145-1151. 

It is known that erythrocytes from patients with sickle cell anemia contain various types of abnormal iron deposits [398], which could be the origin of the overproduction of oxygen radicals in these cells. Indeed, Hebbel et al. [399] has showed that sickle erythrocytes spontaneously generate approximately twice as much superoxide as normal erythrocytes. Later on, it has been shown that these cells are also able to generate hydroxyl radicals catalyzed by three types of iron, preexisting free iron, free iron released during oxidative stress, and iron that cannot be chelated with desferrioxamine [400]. 

It has been proposed that a major source of oxygen radicals in sickle erythrocytes is mutant hemoglobin HbS. However, although HbS showed an accelerated autoxidation rate under in vitro conditions, its in vivo oxidative activity was not determined. Sheng et al. [401] suggested that the observed oxidation rate of HbS is exaggerated by adventitious iron. Dias-Da-Motta et al. [402] proposed that another source of enhanced superoxide production in sickle cells are monocytes in contrast, there is no difference in superoxide release by sickle... 

Beddell, C.R., Goodeord, P.J., Kneen, G., White, R.D., Wilkinson, S., Wootton, R. Substituted benzaldehydes designed to increase the oxygen affinity of human haemoglobin and inhibit the sickling of sickle erythrocytes. Br. J. Pharmacol. 1984 82, 397-407. 

The (Cu,Zn)-SOD levels in erythrocytes of normal human subjects are fairly constant 461 46 (standard deviation) gg/g hemoglobin. Results are also reported for several pathological conditions Small differences were e.g. observed in erythrocytes with on the average a 19 % decrease in patients with Duchenne muscular dystrophy and a 20% increase in black alcoholics in contrast with white alcoholics Sickled erythrocytes showed significantly higher levels of (Cu,Zn)-SOD 170 % on the average of those of normal erythrocytes Tumor cells as a rule seem to have lower or zero levels of (Mn)-SOD... 

Left Normal erythrocytes, Biophoto Associates, Photo Researchers. Right Sickled erythrocytes, Nigel Calder. 

The sample is scanned in the fluorimeter from 560 - 680 nm on excitation at 410 nm. The peak height is measured at 603 nm. Typical results from normal human erythrocyte membranes and sickle erythrocyte membranes compared with non-haem iron levels and total iron measurements are given in Table 4.2 (Hartley and Rice-Evans, 1989). 

Left Normal erythrocytes, C Right Sickled erythrocytes, <... 

The symptoms of sickle cell anemia are due to sequestration and destruction of the abnormal, sickled erythrocytes in the spleen and to the inability of many sickled... 

Kannan, R., Labotka, R., and Low, P. S. (1988). Isolation and characterization of the hemichrome-stabilized membrane protein aggregates from sickle erythrocytes. Major site of autologous antibody binding. J. Biol. Chem. 263,13766-13773. 

FBj. 3. Sickled erythrocytes in oxygen-depleted whole blood from a patient with sickle-cell anemia, demonstrating the similarities in shape to tactoids formed in stroma-free solutions of their deoxygenated hemoglobin. Phase photomiaography, X 375. From John W. Harris, Proc. Soc. Bxptl. Biol, and Med. 75, 197 (1950). 

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