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The Properties of Red Blood Cells from Patients Heterozygous for HbS and HbC (HbSC Genotype).

Hannemann A, Weiss E, Rees DC, Dalibalta S, Ellory JC, Gibson JS - Anemia (2010)

Bottom Line: Their red blood cells (RBCs), containing approximately equal amounts of HbS and HbC, are also likely to show differences in properties which may contribute to disease outcome.Nevertheless, little is known about the behaviour of RBCs from HbSC heterozygotes.Important areas of similarity and potential differences will be emphasised.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.

ABSTRACT
Sickle cell disease (SCD) is one of the commonest severe inherited disorders, but specific treatments are lacking and the pathophysiology remains unclear. Affected individuals account for well over 250,000 births yearly, mostly in the Tropics, the USA, and the Caribbean, also in Northern Europe as well. Incidence in the UK amounts to around 12-15,000 individuals and is increasing, with approximately 300 SCD babies born each year as well as with arrival of new immigrants. About two thirds of SCD patients are homozygous HbSS individuals. Patients heterozygous for HbS and HbC (HbSC) constitute about a third of SCD cases, making this the second most common form of SCD, with approximately 80,000 births per year worldwide. Disease in these patients shows differences from that in homozygous HbSS individuals. Their red blood cells (RBCs), containing approximately equal amounts of HbS and HbC, are also likely to show differences in properties which may contribute to disease outcome. Nevertheless, little is known about the behaviour of RBCs from HbSC heterozygotes. This paper reviews what is known about SCD in HbSC individuals and will compare the properties of their RBCs with those from homozygous HbSS patients. Important areas of similarity and potential differences will be emphasised.

No MeSH data available.


Related in: MedlinePlus

Effect of oxygen tension on the activity of KCl cotransport (KCC) or Psickle in red blood cells (RBCs) from normal individuals or patients with sickle cell disease.  The activity of each transport pathway is normalised—to the value in oxygenated cells (150 mmHg O2) for KCC activity and for that in deoxygenated RBCs (0 mmHg) in the case of Psickle—and given as a percentage.  Solid circles give KCC activity in RBCs from normal HbAA individuals;  open symbols give KCC activity (open circles) or Psickle activity (open triangles) in RBCs from sickle cell patients (HbSS homozygotes).  In these experiments, total magnitude of KCC activity was about 10-fold greater in RBCs from HbSS individuals compared with HbAA ones.  Note how the deoxygenation-induced KCC activity and activation of Psickle follow a similar dependence on O2 tension.  Data taken from [67].
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fig2: Effect of oxygen tension on the activity of KCl cotransport (KCC) or Psickle in red blood cells (RBCs) from normal individuals or patients with sickle cell disease. The activity of each transport pathway is normalised—to the value in oxygenated cells (150 mmHg O2) for KCC activity and for that in deoxygenated RBCs (0 mmHg) in the case of Psickle—and given as a percentage. Solid circles give KCC activity in RBCs from normal HbAA individuals; open symbols give KCC activity (open circles) or Psickle activity (open triangles) in RBCs from sickle cell patients (HbSS homozygotes). In these experiments, total magnitude of KCC activity was about 10-fold greater in RBCs from HbSS individuals compared with HbAA ones. Note how the deoxygenation-induced KCC activity and activation of Psickle follow a similar dependence on O2 tension. Data taken from [67].

Mentions: The first of these, KCC (likely KCC1 and KCC3 isoforms), is more active and abnormally regulated in HbSS cells [38–40]. Mean activity is enhanced >10-fold in unstimulated cells with several stimuli increasing activity further. In normal RBCs, cell swelling is an important trigger of KCC activity [41]. For HbSS cells, however, intracellular pH is probably the most important stimulus in vivo, with KCC activity reaching a peak at about pH 7 [38, 42]. The transporter also responds to O2 tension [43]. In normal red cells, high levels of O2 are required for KCC activity, with the transporter becoming inactivated at low O2. By contrast, in HbSS cells, the transporter remains active during full deoxygenation, thereby allowing it to respond to low pH in hypoxic areas (like active muscle beds) [40] (Figures 1 and 2). KCC is regulated by phosphorylation, through cascades of conjugate protein kinases and phosphatases [44], with differences apparent in HbSS cells compared with HbAA ones, but at present these are poorly defined. The relative deficiency of intracellular Mg2+ in HbSS cells [45, 46] probably acts to increase KCC activity by altering the activity of these regulatory enzymes.


The Properties of Red Blood Cells from Patients Heterozygous for HbS and HbC (HbSC Genotype).

Hannemann A, Weiss E, Rees DC, Dalibalta S, Ellory JC, Gibson JS - Anemia (2010)

Effect of oxygen tension on the activity of KCl cotransport (KCC) or Psickle in red blood cells (RBCs) from normal individuals or patients with sickle cell disease.  The activity of each transport pathway is normalised—to the value in oxygenated cells (150 mmHg O2) for KCC activity and for that in deoxygenated RBCs (0 mmHg) in the case of Psickle—and given as a percentage.  Solid circles give KCC activity in RBCs from normal HbAA individuals;  open symbols give KCC activity (open circles) or Psickle activity (open triangles) in RBCs from sickle cell patients (HbSS homozygotes).  In these experiments, total magnitude of KCC activity was about 10-fold greater in RBCs from HbSS individuals compared with HbAA ones.  Note how the deoxygenation-induced KCC activity and activation of Psickle follow a similar dependence on O2 tension.  Data taken from [67].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3066570&req=5

fig2: Effect of oxygen tension on the activity of KCl cotransport (KCC) or Psickle in red blood cells (RBCs) from normal individuals or patients with sickle cell disease. The activity of each transport pathway is normalised—to the value in oxygenated cells (150 mmHg O2) for KCC activity and for that in deoxygenated RBCs (0 mmHg) in the case of Psickle—and given as a percentage. Solid circles give KCC activity in RBCs from normal HbAA individuals; open symbols give KCC activity (open circles) or Psickle activity (open triangles) in RBCs from sickle cell patients (HbSS homozygotes). In these experiments, total magnitude of KCC activity was about 10-fold greater in RBCs from HbSS individuals compared with HbAA ones. Note how the deoxygenation-induced KCC activity and activation of Psickle follow a similar dependence on O2 tension. Data taken from [67].
Mentions: The first of these, KCC (likely KCC1 and KCC3 isoforms), is more active and abnormally regulated in HbSS cells [38–40]. Mean activity is enhanced >10-fold in unstimulated cells with several stimuli increasing activity further. In normal RBCs, cell swelling is an important trigger of KCC activity [41]. For HbSS cells, however, intracellular pH is probably the most important stimulus in vivo, with KCC activity reaching a peak at about pH 7 [38, 42]. The transporter also responds to O2 tension [43]. In normal red cells, high levels of O2 are required for KCC activity, with the transporter becoming inactivated at low O2. By contrast, in HbSS cells, the transporter remains active during full deoxygenation, thereby allowing it to respond to low pH in hypoxic areas (like active muscle beds) [40] (Figures 1 and 2). KCC is regulated by phosphorylation, through cascades of conjugate protein kinases and phosphatases [44], with differences apparent in HbSS cells compared with HbAA ones, but at present these are poorly defined. The relative deficiency of intracellular Mg2+ in HbSS cells [45, 46] probably acts to increase KCC activity by altering the activity of these regulatory enzymes.

Bottom Line: Their red blood cells (RBCs), containing approximately equal amounts of HbS and HbC, are also likely to show differences in properties which may contribute to disease outcome.Nevertheless, little is known about the behaviour of RBCs from HbSC heterozygotes.Important areas of similarity and potential differences will be emphasised.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.

ABSTRACT
Sickle cell disease (SCD) is one of the commonest severe inherited disorders, but specific treatments are lacking and the pathophysiology remains unclear. Affected individuals account for well over 250,000 births yearly, mostly in the Tropics, the USA, and the Caribbean, also in Northern Europe as well. Incidence in the UK amounts to around 12-15,000 individuals and is increasing, with approximately 300 SCD babies born each year as well as with arrival of new immigrants. About two thirds of SCD patients are homozygous HbSS individuals. Patients heterozygous for HbS and HbC (HbSC) constitute about a third of SCD cases, making this the second most common form of SCD, with approximately 80,000 births per year worldwide. Disease in these patients shows differences from that in homozygous HbSS individuals. Their red blood cells (RBCs), containing approximately equal amounts of HbS and HbC, are also likely to show differences in properties which may contribute to disease outcome. Nevertheless, little is known about the behaviour of RBCs from HbSC heterozygotes. This paper reviews what is known about SCD in HbSC individuals and will compare the properties of their RBCs with those from homozygous HbSS patients. Important areas of similarity and potential differences will be emphasised.

No MeSH data available.


Related in: MedlinePlus