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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2384-2390. Prepublished online as a Blood First Edition Paper on November 13, 2003; DOI 10.1182/blood-2003-01-0237. This Article Full Text (PDF) All Versions of this Article: 2003-01-0237v1 103/6/2384    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Romero, J. R Articles by Fabry, M. E Search for Related Content PubMed PubMed Citation Articles by Romero, J. R Articles by Fabry, M. E Social Bookmarking                   What's this? Submitted January 27, 2003 Accepted November 6, 2003 Exression 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, and Mary E Fabry* Division of Endocrinology, Diabetes, and Hypertension, Harvard Medical School, Boston, MA, USA Department of Medicine, Division of Hematology, Albert Einstein College of Medicine, Bronx, NY, USA * Corresponding author; email: fabry{at}aecom.yu.edu. Elevation of K-Cl cotransport in patients with homozygous HbS or HbC increases red cell 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 knockout mice expressing exclusively human hemoglobin HbC or HbS+, 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+, 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. H. Joiner, R. Kirk Rettig, M. Jiang, M. Risinger, and R. S. Franco Urea stimulation of KCl cotransport induces abnormal volume reduction in sickle reticulocytes Blood, February 15, 2007; 109(4): 1728 - 1735. [Abstract] [Full Text] [PDF]

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