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Rapid increase in red blood cell density driven by K:Cl cotransport in a subset of sickle cell anemia reticulocytes and discocytes.
Blood 1991; 78(1):217-25Blood

Abstract

We have previously demonstrated that young normal (AA) and sickle cell anemia (SS) red blood cells are capable of a volume regulatory decrease response (VRD) driven by a K:Cl cotransporter that is activated by low pH or hypotonic conditions. We now report on the characteristics of young SS cells (SS2, discocytes) capable of rapid increase in density in response to swelling. We have isolated cells with high VRD response (H-VRD) and low VRD response (L-VRD) cells by incubation and density-gradient centrifugation under hypotonic conditions. Comparison of these cells in patients homozygous for hemoglobin (Hb)S indicated that H-VRD cells have 91% more reticulocytes (P less than 9 x 10(-9) than L-VRD cells, 25% less HbF (P less than 5.5 x 10(-5), 106% more NEM (N-methylmaleimide)-stimulated K:Cl cotransport activity (P less than 2 x 10(-4), and 86% more volume-stimulated K:Cl cotransport activity (P less than 1.8 x 10(-3). H-VRD and L-VRD cells have similar G-6-PD and Na+/H+ antiport activity. In agreement with the reduced percent HbF in H-VRD cells, F cells (red blood cells that contain fetal Hb) are depleted from the H-VRD population; however, F reticulocytes are enriched in the H-VRD population to the same extent as non-F reticulocytes, which suggests that both F and non-F reticulocytes have a similar initial distribution of volume-sensitive K:Cl cotransport activity but that it may be more rapidly inactivated in F than in S reticulocytes. We find that H-VRD cells consist of 20% reticulocytes (or 79% of all reticulocytes in SS2) and 80% more mature cells. This study demonstrates the role of K:Cl cotransport in determining red blood cell density, the heterogeneity of K:Cl cotransport activity in reticulocytes, and the capacity for rapid change in the density of reticulocytes with high K:Cl cotransport activity. We speculate that the H-VRD population may be more susceptible to generation of dense and irreversibly sickled cells.

Authors+Show Affiliations

Division of Hematology, Albert Einstein College of Medicine, Bronx, NY 10461.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1712642

Citation

Fabry, M E., et al. "Rapid Increase in Red Blood Cell Density Driven By K:Cl Cotransport in a Subset of Sickle Cell Anemia Reticulocytes and Discocytes." Blood, vol. 78, no. 1, 1991, pp. 217-25.
Fabry ME, Romero JR, Buchanan ID, et al. Rapid increase in red blood cell density driven by K:Cl cotransport in a subset of sickle cell anemia reticulocytes and discocytes. Blood. 1991;78(1):217-25.
Fabry, M. E., Romero, J. R., Buchanan, I. D., Suzuka, S. M., Stamatoyannopoulos, G., Nagel, R. L., & Canessa, M. (1991). Rapid increase in red blood cell density driven by K:Cl cotransport in a subset of sickle cell anemia reticulocytes and discocytes. Blood, 78(1), pp. 217-25.
Fabry ME, et al. Rapid Increase in Red Blood Cell Density Driven By K:Cl Cotransport in a Subset of Sickle Cell Anemia Reticulocytes and Discocytes. Blood. 1991 Jul 1;78(1):217-25. PubMed PMID: 1712642.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Rapid increase in red blood cell density driven by K:Cl cotransport in a subset of sickle cell anemia reticulocytes and discocytes. AU - Fabry,M E, AU - Romero,J R, AU - Buchanan,I D, AU - Suzuka,S M, AU - Stamatoyannopoulos,G, AU - Nagel,R L, AU - Canessa,M, PY - 1991/7/1/pubmed PY - 1991/7/1/medline PY - 1991/7/1/entrez SP - 217 EP - 25 JF - Blood JO - Blood VL - 78 IS - 1 N2 - We have previously demonstrated that young normal (AA) and sickle cell anemia (SS) red blood cells are capable of a volume regulatory decrease response (VRD) driven by a K:Cl cotransporter that is activated by low pH or hypotonic conditions. We now report on the characteristics of young SS cells (SS2, discocytes) capable of rapid increase in density in response to swelling. We have isolated cells with high VRD response (H-VRD) and low VRD response (L-VRD) cells by incubation and density-gradient centrifugation under hypotonic conditions. Comparison of these cells in patients homozygous for hemoglobin (Hb)S indicated that H-VRD cells have 91% more reticulocytes (P less than 9 x 10(-9) than L-VRD cells, 25% less HbF (P less than 5.5 x 10(-5), 106% more NEM (N-methylmaleimide)-stimulated K:Cl cotransport activity (P less than 2 x 10(-4), and 86% more volume-stimulated K:Cl cotransport activity (P less than 1.8 x 10(-3). H-VRD and L-VRD cells have similar G-6-PD and Na+/H+ antiport activity. In agreement with the reduced percent HbF in H-VRD cells, F cells (red blood cells that contain fetal Hb) are depleted from the H-VRD population; however, F reticulocytes are enriched in the H-VRD population to the same extent as non-F reticulocytes, which suggests that both F and non-F reticulocytes have a similar initial distribution of volume-sensitive K:Cl cotransport activity but that it may be more rapidly inactivated in F than in S reticulocytes. We find that H-VRD cells consist of 20% reticulocytes (or 79% of all reticulocytes in SS2) and 80% more mature cells. This study demonstrates the role of K:Cl cotransport in determining red blood cell density, the heterogeneity of K:Cl cotransport activity in reticulocytes, and the capacity for rapid change in the density of reticulocytes with high K:Cl cotransport activity. We speculate that the H-VRD population may be more susceptible to generation of dense and irreversibly sickled cells. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/1712642/Rapid_increase_in_red_blood_cell_density_driven_by_K:Cl_cotransport_in_a_subset_of_sickle_cell_anemia_reticulocytes_and_discocytes_ L2 - http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=1712642 DB - PRIME DP - Unbound Medicine ER -