Erythrocytes sickle cells

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

In sickle cell hemoglobin (HbS), Val replaces the P6 Glu of HbA, creating a sticky patch that has a complement on deoxyHb (but not on oxyHb). De-oxyHbS polymerizes at low O2 concentrations, forming fibers that distort erythrocytes into sickle shapes. 

Chisolm JJ Jr, Brown DH. 1979. Micromethod for zinc protoporphyrin in erythrocytes Including new data on the absorptivity of zinc protoporphyrin and new observation in neonates and sickle cell disease. Biochem Med 22 214-237. 

Although ICAM-1 seems not to be involved in the sickle cell adhesion to vascular endothelium, it may exacerbate vasoocclusion by promoting leukocyte adhesion. In this context, it is remarkable to note that in HU-treated SCA patients, the strongest correlation was found between total white cell count and severity of crisis rather than with erythrocyte-related parameters [28]. The current consensus is that leukocyte endothelium adhesion may initiate vasoocclusion followed by RBC sequestration and entrapment in the microvascular lumen with ensuing painful crisis. Thus overexpression of ICAM-1 is expected to promote VOC. The data... 

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... 

Clearly this patient has both clinical and haematological symptoms of severe anaemia. The cause is too few red cells low RBC count and PCV but the erythrocytes which are present contain a higher than usual concentration of haemoglobin (MCHC result). Iron deficiency and vitamin B12 deficiency can be ruled out by the high serum ferritin and normal MCV results respectively. The negative HbS screen rules out sickle cell anaemia which is fairly common in Africans. 

The sickled shape of erythrocytes in patients with sickle cell anemia occurs because of the tendency for HbS to polymerize. HbS differs from HbA by substitution of a solvent-exposed glutamate by valine in 3-globin, which forms a sticky patch that promotes abrogation and polymerization of the protein. 

In the majority of patients with sickle cell disease, anemia is not the major problem the anemia is generally well compensated even though such individuals have a chronically low hematocrit (20-30%), a low serum hemoglobin level (7-10 g/dL), and an elevated reticulocyte count. Instead, the primary problem is that deoxygenated HbS chains form polymeric structures that dramatically change erythrocyte shape, reduce deformability, and elicit membrane permeability changes that further promote hemoglobin polymerization. Abnormal erythrocytes... 

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... 

FIGURE 5-19 A comparison of uniform, cup-shaped, normal erythrocytes (a) with the variably shaped erythrocytes seen in sickle-cell anemia (b), which range from normal to spiny or sickle-shaped. 

Sickle-cell anemia, as we have noted, occurs in individuals homozygous for the sickle-cell allele of the gene encoding the )3 subunit of hemoglobin. Individuals who receive the sickle-cell allele from only one parent and are thus heterozygous experience a milder condition called sickle-cell trait only about 1% of their erythrocytes become sickled on deoxygenation. These individuals may live completely normal lives if they avoid vigorous exercise or other stresses on the circulatory system. 

Reported applications of DMA include the cross-linking of bovine pancreatic ribonuclease A (Hartman and Wold, 1967), treatment of erythrocyte membranes to reduce the effects of sickle cell anemia (Waterman et al., 1975), conjugation and analysis of the outer membrane proteins of Neisseria gonorrhoeae (Newhall et al., 1980), protein structural studies of bovine a-crystalline (Siezen et al., 1980), cross-linking of hemoglobin S (Pennathur-Das et al., 1982), and forming S-carbomethoxy-valeramidine during hydrolysis of DMA (Mentzer et al., 1982). 

The test is illustrated with results taken from experiments on membranes of erythrocytes from patients with sickle cell anaemia, which tend to retain increased levels of membrane-associated iron, compared with those of normal erythrocytes. Some results are shown in Table 4.2. 

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