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Novel permeability characteristics of red blood cells from sickle cell patients heterozygous for HbS and HbC (HbSC genotype).
Blood Cells Mol Dis. 2010 Jun 15; 45(1):46-52.BC

Abstract

Individuals heterozygous for HbS and HbC (HbSC) represent about 1/3(rd) of sickle cell disease (SCD) patients. Whilst HbSC disease is generally milder, there is considerable overlap in symptoms with HbSS disease. HbSC patients, as well as HbSS ones, present with the chronic anaemia and panoply of acute vaso-occlusive complications that characterize SCD. However, there are important clinical and haematological differences. Certain complications occur with greater frequency in HbSC patients (like proliferative retinopathy and osteonecrosis) whilst intravascular haemolysis is reduced. Patients with HbSC disease can be considered as a discrete subset of SCD cases. Although much work has been carried out on understanding the pathogenesis of SCD in HbSS homozygotes, including the contribution of altered red blood cell permeability, relatively little pertains directly to HbSC individuals. Results reported in the literature suggest that HbSC cells, and particularly certain subpopulations, present with similar permeability to HbSS cells but there are also important differences - these have not been well characterized. We hypothesise that their unique cell transport properties accounts for the different pattern of disease in HbSC patients and represents a potential chemotherapeutic target not shared in red blood cells from HbSS patients. The distinct pattern of clinical haematology in HbSC disease is emphasised here. We analyse some of the electrophysiological properties of single red blood cells from HbSC patients, comparing them with those from HbSS patients and normal HbAA individuals. We also use the isosmotic haemolysis technique to investigate the behaviour of total red blood cell populations. Whilst both HbSS and HbSC cells show increased monovalent and divalent (Ca(2+)) cation conductance further elevated upon deoxygenation, the distribution of current magnitudes differs, and outward rectification is greatest for HbSC cells. In addition, although Gd(3+) largely abolishes the cation conductance of both HbSS and HbSC cells, only in HbSS ones are currents inhibited by the aminoglycosides like streptomycin. This distinction is retained in isosmotic lysis experiments where both HbSS and HbSC cells undergo haemolysis in sucrose solutions but streptomycin significantly inhibits lysis only in HbSS cells. These findings emphasise similarities but also differences in the permeability properties of HbSS and HbSC cells, which may be important in pathogenesis.

Authors+Show Affiliations

Department of Physiology, Anatomy & Genetics, Parks Road, Oxford, OX1 3PT, UK. sarah.dalibalta@dpag.ox.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20227897

Citation

Dalibalta, S, et al. "Novel Permeability Characteristics of Red Blood Cells From Sickle Cell Patients Heterozygous for HbS and HbC (HbSC Genotype)." Blood Cells, Molecules & Diseases, vol. 45, no. 1, 2010, pp. 46-52.
Dalibalta S, Ellory JC, Browning JA, et al. Novel permeability characteristics of red blood cells from sickle cell patients heterozygous for HbS and HbC (HbSC genotype). Blood Cells Mol Dis. 2010;45(1):46-52.
Dalibalta, S., Ellory, J. C., Browning, J. A., Wilkins, R. J., Rees, D. C., & Gibson, J. S. (2010). Novel permeability characteristics of red blood cells from sickle cell patients heterozygous for HbS and HbC (HbSC genotype). Blood Cells, Molecules & Diseases, 45(1), 46-52. https://doi.org/10.1016/j.bcmd.2010.02.010
Dalibalta S, et al. Novel Permeability Characteristics of Red Blood Cells From Sickle Cell Patients Heterozygous for HbS and HbC (HbSC Genotype). Blood Cells Mol Dis. 2010 Jun 15;45(1):46-52. PubMed PMID: 20227897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel permeability characteristics of red blood cells from sickle cell patients heterozygous for HbS and HbC (HbSC genotype). AU - Dalibalta,S, AU - Ellory,J C, AU - Browning,J A, AU - Wilkins,R J, AU - Rees,D C, AU - Gibson,J S, Y1 - 2010/03/15/ PY - 2009/12/31/received PY - 2010/01/19/accepted PY - 2010/3/16/entrez PY - 2010/3/17/pubmed PY - 2010/9/10/medline SP - 46 EP - 52 JF - Blood cells, molecules & diseases JO - Blood Cells Mol Dis VL - 45 IS - 1 N2 - Individuals heterozygous for HbS and HbC (HbSC) represent about 1/3(rd) of sickle cell disease (SCD) patients. Whilst HbSC disease is generally milder, there is considerable overlap in symptoms with HbSS disease. HbSC patients, as well as HbSS ones, present with the chronic anaemia and panoply of acute vaso-occlusive complications that characterize SCD. However, there are important clinical and haematological differences. Certain complications occur with greater frequency in HbSC patients (like proliferative retinopathy and osteonecrosis) whilst intravascular haemolysis is reduced. Patients with HbSC disease can be considered as a discrete subset of SCD cases. Although much work has been carried out on understanding the pathogenesis of SCD in HbSS homozygotes, including the contribution of altered red blood cell permeability, relatively little pertains directly to HbSC individuals. Results reported in the literature suggest that HbSC cells, and particularly certain subpopulations, present with similar permeability to HbSS cells but there are also important differences - these have not been well characterized. We hypothesise that their unique cell transport properties accounts for the different pattern of disease in HbSC patients and represents a potential chemotherapeutic target not shared in red blood cells from HbSS patients. The distinct pattern of clinical haematology in HbSC disease is emphasised here. We analyse some of the electrophysiological properties of single red blood cells from HbSC patients, comparing them with those from HbSS patients and normal HbAA individuals. We also use the isosmotic haemolysis technique to investigate the behaviour of total red blood cell populations. Whilst both HbSS and HbSC cells show increased monovalent and divalent (Ca(2+)) cation conductance further elevated upon deoxygenation, the distribution of current magnitudes differs, and outward rectification is greatest for HbSC cells. In addition, although Gd(3+) largely abolishes the cation conductance of both HbSS and HbSC cells, only in HbSS ones are currents inhibited by the aminoglycosides like streptomycin. This distinction is retained in isosmotic lysis experiments where both HbSS and HbSC cells undergo haemolysis in sucrose solutions but streptomycin significantly inhibits lysis only in HbSS cells. These findings emphasise similarities but also differences in the permeability properties of HbSS and HbSC cells, which may be important in pathogenesis. SN - 1096-0961 UR - https://www.unboundmedicine.com/medline/citation/20227897/Novel_permeability_characteristics_of_red_blood_cells_from_sickle_cell_patients_heterozygous_for_HbS_and_HbC__HbSC_genotype__ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1079-9796(10)00044-6 DB - PRIME DP - Unbound Medicine ER -