Rapid increase in red blood cell density driven by K

Cl cotransport in a subset of sickle cell anemia reticulocytes and discocytes

Mary E. Fabry, Jose R. Romero, Iris D. Buchanan, Sandra M. Suzuka, George Stamatoyannopoulos, Ronald L. Nagel, Mitzy Canessa

Research output: Contribution to journalArticle

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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:CI 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 < 9 × 10-9) than L-VRD cells, 25% less HbF (P < 5.5 × 10-5), 106% more NEM (N-methylmaleimide)-stimulated K:CI cotransport activity (P < 2 ×10-4), and 86% more volume-stimulated K:CI cotransport activity (P < 1.8 × 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:CI 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:CI cotransport in determining red blood cell density, the heterogeneity of K:CI cotransport activity in reticulocytes, and the capacity for rapid change in the density of reticulocytes with high K:CI cotransport activity. We speculate that the H-VRD population may be more susceptible to generation of dense and irreversibly sickled cells.

Original languageEnglish (US)
Pages (from-to)217-225
Number of pages9
JournalBlood
Volume78
Issue number1
StatePublished - Jul 1 1991
Externally publishedYes

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Reticulocytes
Sickle Cell Anemia
Blood
Cell Count
Erythrocytes
Cells
Sickle Hemoglobin
Fetal Hemoglobin
Centrifugation
Swelling
Population
Density Gradient Centrifugation
Ion Transport

ASJC Scopus subject areas

  • Hematology

Cite this

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), 217-225.

Rapid increase in red blood cell density driven by K : Cl cotransport in a subset of sickle cell anemia reticulocytes and discocytes. / Fabry, Mary E.; Romero, Jose R.; Buchanan, Iris D.; Suzuka, Sandra M.; Stamatoyannopoulos, George; Nagel, Ronald L.; Canessa, Mitzy.

In: Blood, Vol. 78, No. 1, 01.07.1991, p. 217-225.

Research output: Contribution to journalArticle

Fabry, ME, Romero, JR, Buchanan, ID, Suzuka, SM, Stamatoyannopoulos, G, Nagel, RL & 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, vol. 78, no. 1, pp. 217-225.
Fabry ME, Romero JR, Buchanan ID, Suzuka SM, Stamatoyannopoulos G, Nagel RL 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):217-225.
Fabry, Mary E. ; Romero, Jose R. ; Buchanan, Iris D. ; Suzuka, Sandra M. ; Stamatoyannopoulos, George ; Nagel, Ronald L. ; Canessa, Mitzy. / Rapid increase in red blood cell density driven by K : Cl cotransport in a subset of sickle cell anemia reticulocytes and discocytes. In: Blood. 1991 ; Vol. 78, No. 1. pp. 217-225.
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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:CI 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 < 9 × 10-9) than L-VRD cells, 25{\%} less HbF (P < 5.5 × 10-5), 106{\%} more NEM (N-methylmaleimide)-stimulated K:CI cotransport activity (P < 2 ×10-4), and 86{\%} more volume-stimulated K:CI cotransport activity (P < 1.8 × 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:CI 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:CI cotransport in determining red blood cell density, the heterogeneity of K:CI cotransport activity in reticulocytes, and the capacity for rapid change in the density of reticulocytes with high K:CI cotransport activity. We speculate that the H-VRD population may be more susceptible to generation of dense and irreversibly sickled cells.",
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