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

Division of Endocrinology, Diabetes and Hypertension, Harvard Medical School, Boston, MA, USA.
Blood (Impact Factor: 10.45). 04/2004; 103(6):2384-90. DOI: 10.1182/blood-2003-01-0237
Source: PubMed


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+ gamma, 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+ gamma, 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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Available from: Mary Fabry, Oct 09, 2015
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    • "Seven week old C57BL/6J or human hemoglobin transgenic α H β A mice that were hemizygous for the transgene (Romero et al., 2004), but had no knock-outs or deletions, were infected retroorbitaly with ~10 7 CFU grown to mid-log phase in tryptic soy broth and resuspended in sterile PBS. Ninety-six hours post infection the mice were euthanized with forced inhalation of CO 2 . "
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