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Evidence for a direct reticulocyte origin of dense red cells in sickle cell anemia.
J Clin Invest 1991; 87(1):113-24JCI

Abstract

To explore our hypothesis of a direct reticulocyte origin of irreversibly sickled cells (ISCs), we fractionated light, reticulocyte-rich, and discocyte-rich sickle anemia red cells on Stractan gradients, and examined the effects of deoxygenation-induced sickling, external Ca2+, acidification, and replacing external Na+ by impermeant N-methyl-D-glucamine (NMG+). Sickling permeabilized light reticulocyte-rich cells to cations (Na+, K+, and Ca2+) more than discocytes; without external Ca2+, Na+ influx matched K+ efflux, with stable cell volume; with Ca2+, many light, low hemoglobin (Hb) F reticulocytes dehydrated rapidly (preventable by quinine, a Ca2(+)-dependent K+ channel inhibitor). Acidification of oxygenated discocytes (high mean Hb F) and reticulocyte-rich fractions yielded denser, reticulocyte-enriched cells with lower Hb F (as in light reticulocyte or dense ISC-rich fractions). Light cells shrank when NMG+ replaced Na+, supporting predictions of a Na(+)-dependent volume control system. Demonstration of sickling-induced, Ca2(+)-dependent dehydration of Hb F-free reticulocytes, and conservation of acid-stimulated K:Cl cotransport among low Hb F, reticulocyte-enriched cells in discocyte fractions support the hypothesis. Ancillary new findings included heparin stimulation of sickling-induced Na+ and K+ permeabilizations, and Ca2+ inhibition of the Na+ leak.

Authors+Show Affiliations

Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

1702096

Citation

Bookchin, R M., et al. "Evidence for a Direct Reticulocyte Origin of Dense Red Cells in Sickle Cell Anemia." The Journal of Clinical Investigation, vol. 87, no. 1, 1991, pp. 113-24.
Bookchin RM, Ortiz OE, Lew VL. Evidence for a direct reticulocyte origin of dense red cells in sickle cell anemia. J Clin Invest. 1991;87(1):113-24.
Bookchin, R. M., Ortiz, O. E., & Lew, V. L. (1991). Evidence for a direct reticulocyte origin of dense red cells in sickle cell anemia. The Journal of Clinical Investigation, 87(1), pp. 113-24.
Bookchin RM, Ortiz OE, Lew VL. Evidence for a Direct Reticulocyte Origin of Dense Red Cells in Sickle Cell Anemia. J Clin Invest. 1991;87(1):113-24. PubMed PMID: 1702096.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence for a direct reticulocyte origin of dense red cells in sickle cell anemia. AU - Bookchin,R M, AU - Ortiz,O E, AU - Lew,V L, PY - 1991/1/1/pubmed PY - 1991/1/1/medline PY - 1991/1/1/entrez SP - 113 EP - 24 JF - The Journal of clinical investigation JO - J. Clin. Invest. VL - 87 IS - 1 N2 - To explore our hypothesis of a direct reticulocyte origin of irreversibly sickled cells (ISCs), we fractionated light, reticulocyte-rich, and discocyte-rich sickle anemia red cells on Stractan gradients, and examined the effects of deoxygenation-induced sickling, external Ca2+, acidification, and replacing external Na+ by impermeant N-methyl-D-glucamine (NMG+). Sickling permeabilized light reticulocyte-rich cells to cations (Na+, K+, and Ca2+) more than discocytes; without external Ca2+, Na+ influx matched K+ efflux, with stable cell volume; with Ca2+, many light, low hemoglobin (Hb) F reticulocytes dehydrated rapidly (preventable by quinine, a Ca2(+)-dependent K+ channel inhibitor). Acidification of oxygenated discocytes (high mean Hb F) and reticulocyte-rich fractions yielded denser, reticulocyte-enriched cells with lower Hb F (as in light reticulocyte or dense ISC-rich fractions). Light cells shrank when NMG+ replaced Na+, supporting predictions of a Na(+)-dependent volume control system. Demonstration of sickling-induced, Ca2(+)-dependent dehydration of Hb F-free reticulocytes, and conservation of acid-stimulated K:Cl cotransport among low Hb F, reticulocyte-enriched cells in discocyte fractions support the hypothesis. Ancillary new findings included heparin stimulation of sickling-induced Na+ and K+ permeabilizations, and Ca2+ inhibition of the Na+ leak. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/1702096/Evidence_for_a_direct_reticulocyte_origin_of_dense_red_cells_in_sickle_cell_anemia_ L2 - https://doi.org/10.1172/JCI114959 DB - PRIME DP - Unbound Medicine ER -