Expression of HbC and HbS, but not HbA, results in activation of K-Cl cotransport activity in transgenic mouse red cells

Jose R. Romero, Sandra M. Suzuka, Ronald L. Nagel, Mary E. Fabry

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Elevation of K-Cl cotransport in patients with homozygous hemoglobin (Hb) S or HbC increases red cell mean corpuscular hemoglobin concentration (MCHC) and contributes significantly to pathology. Elucidation of the origin of elevated K-Cl cotransport In red cells with mutant hemoglobins has been confounded by the concomitant presence of reticulocytes with high K-Cl cotransport. In red cells of control mice (C57BL), transgenic mice that express only human HbA, and transgenic mice that express both mouse globins and human HbS, volume stimulation is weak and insensitive to NO3- and dihydroindenyl-oxy-alkanoic acid (DIOA). DIOA and NO3- are inhibitors in all other mammalian red cells. In contrast, in knock-out mice expressing exclusively human hemoglobin HbC or HbS+γ, replacement of isotonic Cl- media by hypotonic Cl- resulted in strong volume stimulation and sensitivity to DIOA, okadaic acid, and NO3-. In summary, we find that HbC, under all conditions, and HbS+γ, In the absence of mouse globins, have significant quantitative and qualitative effects on K-Cl cotransport In mouse red cells and activate mouse K-Cl. We conclude that human globins are able to stimulate the activity and/or regulation of K-Cl cotransport In mouse red cells. These observations support the contention that HbS and HbC stimulate K-Cl cotransport in human red cells.

Original languageEnglish (US)
Pages (from-to)2384-2390
Number of pages7
JournalBlood
Volume103
Issue number6
DOIs
StatePublished - Mar 15 2004
Externally publishedYes

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Transgenic Mice
Chemical activation
Cells
Globins
Hemoglobins
Sickle Hemoglobin
Okadaic Acid
Erythrocyte Indices
Reticulocytes
Pathology
Inbred C57BL Mouse
Knockout Mice
((dihydroindenyl)oxy)alkanoic acid

ASJC Scopus subject areas

  • Hematology

Cite this

Expression of HbC and HbS, but not HbA, results in activation of K-Cl cotransport activity in transgenic mouse red cells. / Romero, Jose R.; Suzuka, Sandra M.; Nagel, Ronald L.; Fabry, Mary E.

In: Blood, Vol. 103, No. 6, 15.03.2004, p. 2384-2390.

Research output: Contribution to journalArticle

Romero, Jose R. ; Suzuka, Sandra M. ; Nagel, Ronald L. ; Fabry, Mary E. / Expression of HbC and HbS, but not HbA, results in activation of K-Cl cotransport activity in transgenic mouse red cells. In: Blood. 2004 ; Vol. 103, No. 6. pp. 2384-2390.
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abstract = "Elevation of K-Cl cotransport in patients with homozygous hemoglobin (Hb) S or HbC increases red cell mean corpuscular hemoglobin concentration (MCHC) and contributes significantly to pathology. Elucidation of the origin of elevated K-Cl cotransport In red cells with mutant hemoglobins has been confounded by the concomitant presence of reticulocytes with high K-Cl cotransport. In red cells of control mice (C57BL), transgenic mice that express only human HbA, and transgenic mice that express both mouse globins and human HbS, volume stimulation is weak and insensitive to NO3- and dihydroindenyl-oxy-alkanoic acid (DIOA). DIOA and NO3- are inhibitors in all other mammalian red cells. In contrast, in knock-out mice expressing exclusively human hemoglobin HbC or HbS+γ, replacement of isotonic Cl- media by hypotonic Cl- resulted in strong volume stimulation and sensitivity to DIOA, okadaic acid, and NO3-. In summary, we find that HbC, under all conditions, and HbS+γ, In the absence of mouse globins, have significant quantitative and qualitative effects on K-Cl cotransport In mouse red cells and activate mouse K-Cl. We conclude that human globins are able to stimulate the activity and/or regulation of K-Cl cotransport In mouse red cells. These observations support the contention that HbS and HbC stimulate K-Cl cotransport in human red cells.",
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