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

Blood ◽  
2004 ◽  
Vol 103 (6) ◽  
pp. 2384-2390 ◽  
Author(s):  
Jose R. Romero ◽  
Sandra M. Suzuka ◽  
Ronald L. Nagel ◽  
Mary E. Fabry
Keyword(s):  
Transgenic Mice ◽  
Hemoglobin Concentration ◽  
Red Cells ◽  
Mean Corpuscular Hemoglobin ◽  
Red Cell ◽  
Knock Out ◽  
High K ◽  
Hb S ◽  
Knock Out Mice ◽  
Human Red Cells

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.

Roles of cell geometry and cellular viscosity in red cell passage through narrow pores

1985 ◽  
Vol 248 (5) ◽  
pp. C473-C479 ◽  
Author(s):  
W. H. Reinhart ◽  
S. Chien
Keyword(s):  
Pore Size ◽  
Hemoglobin Concentration ◽  
Red Cells ◽  
Mean Corpuscular Hemoglobin ◽  
Red Cell ◽  
Cell Passage ◽  
Cell Deformability ◽  
Red Cell Deformability ◽  
Narrow Channels ◽  
The Mean

The relative roles of two fundamental determinants of red cell deformability, namely cell size and cellular viscosity, in affecting red cell passage through narrow channels have been assessed by determining the filterability of red cells subjected to osmotic variations. Suspensions of red cells (10(6) cells/microliter) in eight different osmolalities ranging from 172 +/- 3 (mean +/- SD) to 665 +/- 28 mosmol/kg H2O were filtered through polycarbonate sieves with three different pore diameters (2.6 +/- 0.2, 4.5 +/- 0.6, and 6.9 +/- 0.8 micron). The mean corpuscular volume varied inversely with osmolality and ranged from 149 +/- 9 to 67 +/- 10 fl; the mean corpuscular hemoglobin concentration varied directly with osmolality and ranged from 23.7 +/- 0.8 to 55.9 +/- 3.9 g/dl. The filtration data were analyzed with a theoretical model to derive the parameter beta, which is the ratio of resistance in a pore bearing a red blood cell to that in a pore filled with the suspending medium alone. For each pore size, beta showed a V-shaped relationship with osmolality; the optimum osmolality for minimum beta varied inversely with the pore size. For the small 2.6-micron pores, the minimum beta was attained following hyperosmotic shrinkage of the red cells at 400 mosmol/kg H2O, whereas passage through the large 6.9-micron pores was facilitated by hypoosmotic swelling of the red cells in about 200 mosmol/kg H2O. Red cell filtration through small pores is more sensitive to alterations in cell volume, whereas that through large pores is primarily determined by changes in cellular viscosity.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals THE VARIATION IN THE CORPUSCULAR HEMOGLOBIN CONCENTRATION IN THE HUMAN RED CELL, AS MEASURED BY DENSITOMETRY

1955 ◽  
Vol 39 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Eric Ponder ◽  
Delia Barreto
Keyword(s):  
Coefficient Of Variation ◽  
Hemoglobin Concentration ◽  
Red Cells ◽  
Red Cell ◽  
Corpuscular Hemoglobin ◽  
Volume Changes ◽  
Spherical Form ◽  
Average Hemoglobin ◽  
Individual Human ◽  
Human Red Cells

This paper deals with measurement of the hemoglobin concentration in individual human red cells, the concentration being measured as a function of the optical density, at 5461 A, of the central part of the cell in its spherical form. A number of technical difficulties, principally concerned with the effects of focus, have been met with, and these are described in detail. The results show that the coefficient of variation of the hemoglobin concentration is relatively small (about 5.5 per cent) in the case of fresh human red cells in ACD solution, that the coefficient of variation is almost doubled when the red cells have been stored for 6 weeks at 4°C. or when heparin is used as an anticoagulant instead of ACD solution, but that the average hemoglobin concentration is substantially the same in all three cases. The increase in the coefficient of variation found when the red cells have been stored or when heparin is used is probably due to volume changes, some cells shrinking while others swell.

scholarly journals Kinetics and stoichiometry of Na-dependent Li transport in human red blood cells.

1978 ◽  
Vol 72 (2) ◽  
pp. 249-265 ◽  
Author(s):  
B Sarkadi ◽  
J K Alifimoff ◽  
R B Gunn ◽  
D C Tosteson
Keyword(s):  
Transport System ◽  
Red Cells ◽  
Normal Male ◽  
Red Cell ◽  
Red Cell Membrane ◽  
Human Red Blood Cells ◽  
Na Efflux ◽  
Tightly Coupled ◽  
Male Subjects ◽  
Human Red Cells

This paper describes the kinetics and stoichiometry of a tightly coupled Na-Li exchange transport system in human red cells. The system is inhibited by phloretin and furosemide but not by ouabain. Li influx by this system increases and saturates with increasing concentrations of external Li and internal Na and is inhibited competitively by external Na. Comparable functions relate Li efflux and Na efflux to internal and external Li and Na concentrations. Analysis of these relations yields the following values for the ion concentrations required to half-maximally activate the transport system: internal Na and Li 9.0 and 0.5 mM, respectively, external Na and Li 25 and 1.5 mM, respectively. The system performs a 1:1 exchange of Na and Li moving in opposite directions across the red cell membrane. We found no evidence for a simultaneous transport of more than one Na and Li by the system. The maximum transport rate of Na-dependent Li transport varied between 0.1 and 0.37 mmol/(liter of cells X h) in the red cells of the five normal male subjects studied. No significant variations between individual subjects were observed for bicarbonate-stimulated Li transport and for the residual Li fluxes which occur in the absence of bicarbonate and in the presence of ouabain plus phloretin.

Acetylcholinesterase in Human Erythroid Cells

1973 ◽  
Vol 12 (3) ◽  
pp. 911-923
Author(s):  
R. J. SKAER
Keyword(s):  
Endoplasmic Reticulum ◽  
Nervous System ◽  
Golgi Apparatus ◽  
Red Cells ◽  
The Other ◽  
Red Cell ◽  
Erythroid Cells ◽  
Cell Replacement ◽  
Kinetics Of ◽  
Human Red Cells

Acetylcholinesterase is present in human red cells but cannot be demonstrated by the copper thiocholine test. The enzyme is revealed, however, in the perinuclear cisterna, endoplasmic reticulum and Golgi apparatus of red cell precursors. It is suggested that 2 forms of the enzyme are present, one of which can be demonstrated by the copper thiocholine test, the other cannot; one form may be the precursor of the other. These observations may cast light on the kinetics of red cell replacement and on the interpretation of the results from the copper thiocholine test on other tissues such as the nervous system.

Biological Activity of a Semisynthetic Flavonoid, O-(β-Hydroxyethyl)rutoside: Light-Scattering and Metabolic Studies of Human Red Cells and Platelets

1973 ◽  
Vol 19 (1) ◽  
pp. 31-35 ◽  
Author(s):  
J W ten Cate ◽  
N J van Haeringen ◽  
J Gerritsen ◽  
E Glasius
Keyword(s):  
Biological Activity ◽  
Light Scattering ◽  
Platelet Aggregation ◽  
Cell Aggregation ◽  
Red Cells ◽  
Red Cell ◽  
High Concentrations ◽  
Platelet Functions ◽  
Human Red Cells ◽  
Red Cell Aggregation

Abstract The effect of O-(β-hydroxyethyl)-rutoside (HR) on human erythrocyte and platelet functions is reported. Only high concentrations of the compound distinctly inhibited red cell and platelet aggregation induced by ADP and epinephrine. Lower concentrations of HR inhibit [14C8]adenosine incorporation into red cells as well as into platelets. Inhibition occurs at both 0°C and 37°C, presumably because diffusion of [14C8]adenosine is hindered. Phosphorylation of [14C8] adenosine by the platelets is not inhibited by HR. The inhibition of red cell aggregation is reversed by washing the cells with plasma. Collectively, these findings indicate an effect of the compound at the site of the membrane, independent of cellular metabolism

scholarly journals Effects Produced by Trypsin on Certain Properties of the Human Red Cell

Blood ◽  
1951 ◽  
Vol 6 (4) ◽  
pp. 350-356 ◽  
Author(s):  
ERIC PONDER
Keyword(s):  
Cell Surface ◽  
Electrophoretic Mobility ◽  
Red Cells ◽  
Red Cell ◽  
Surface Ultrastructure ◽  
Related Enzyme ◽  
Protein Components ◽  
Human Red Cells

Abstract Human red cells treated with trypsin in such a way as to become agglutinable in the presence of incomplete antibodies are affected in certain other respects. Their volume is slightly increased, their ghosts are unusually rigid or "volume-occupying," their osmotic and mechanical fragilities are slightly increased and their electrophoretic mobility is reduced. These changes are probably due to effects on the protein components of the red cell surface ultrastructure. Similar effects are also produced by the related enzyme mexacain.

scholarly journals Antisickling effect of tellurite: a potent membrane-acting agent in vitro

Blood ◽  
1984 ◽  
Vol 64 (1) ◽  
pp. 305-307 ◽  
Author(s):  
T Asakura ◽  
Y Shibutani ◽  
MP Reilly ◽  
RH DeMeio
Keyword(s):  
Hemoglobin Concentration ◽  
Inhibitory Effect ◽  
Red Cells ◽  
Cell Swelling ◽  
Red Cell ◽  
Red Cell Membrane ◽  
Potassium Tellurite ◽  
New Type ◽  
Acting Agent

Abstract Potassium tellurite (K2TeO3) was found to be a potent antisickling agent that inhibited red cell sickling at concentrations less than 10 mumol/L. The inhibitory effect depended on the incubation time, with the effect increasing with longer incubation periods. Because tellurite causes swelling of red cells, and because the antisickling effect of tellurite correlated with the degree of red cell swelling, the antisickling effect of tellurite is assumed to be due to the decreased mean cell hemoglobin concentration. Swelling of red cells by tellurite was accelerated by the addition of reduced glutathione. Tellurite appears to be a new type of antisickling agent that interacts with the red cell membrane.

Blood-perfused working isolated rat heart

1976 ◽  
Vol 41 (4) ◽  
pp. 603-607 ◽  
Author(s):  
M. A. Duvelleroy ◽  
M. Duruble ◽  
J. L. Martin ◽  
B. Teisseire ◽  
J. Droulez ◽  
...  
Keyword(s):  
Rat Heart ◽  
Coronary Flow ◽  
Myocardial Oxygen Consumption ◽  
Isolated Rat Heart ◽  
Red Cells ◽  
Red Cell ◽  
External Work ◽  
Bicarbonate Buffer ◽  
Isolated Rat ◽  
Human Red Cells

We describe a method for perfusion of a working isolated rat heart with washed erythrocytes suspended in a Krebs-Henseleit bicarbonate buffer containing bovine albumin (fraction V). With washed pig red cells, as hematocritwas varied between 0 and 40%, coronary flow (CF), aortic flow (AF), external work (W), and myocardial oxygen consumption (MVO2) were measured. Hemodynamic data at a hematocrit of 30% (CF = 5.4 +/- 0.7 ml/min per g, AF = 75 +/- 8 ml/min per g) were identical with those reported for the intact animal.Coronary sinus PO2 was highest with a red cell-free perfusate suggesting that coronary flow is partially shunted. Human red cells obtained from bankedblood, were tried also with success. With careful filtration, the preparation is stable for 2 h and well suited for study of the dynamics of myocardial oxygen delivery.

Tr: A Canine Red Cell Antigen Related to the A-antigen of Human Red Cells

Vox Sanguinis ◽  
1971 ◽  
Vol 20 (6) ◽  
pp. 542-554
Author(s):  
A.J. Bowdler ◽  
R.W. Bull ◽  
R. Slating ◽  
S.N. Swisher
Keyword(s):  
Red Cells ◽  
Red Cell ◽  
Cell Antigen ◽  
Human Red Cells

Estradiol transport by human red cells

1960 ◽  
Vol 15 (3) ◽  
pp. 515-519 ◽  
Author(s):  
Fritz Bischoff ◽  
George Bryson
Keyword(s):  
Water Solubility ◽  
Intact Cell ◽  
Red Cells ◽  
Red Cell ◽  
Cell Penetration ◽  
Hemoglobin Content ◽  
Hemoglobin Solution ◽  
Low Concentration ◽  
Cell Affinity ◽  
Human Red Cells

Experiments were designed to establish whether the estrogens penetrate the membrane of the red cells or are transported by it. By hemolyzing red cells and reconditioning the ghosts, it was shown that the enzyme, estronase, follows the hemoglobin and therefore indicates that estrone and estradiol penetrate the membrane. Distribution of estradiol between intact red cells or reconditioned ghosts and ghost-free hemolysates of red cells or crystallized hemoglobin solution was proportional to the hemoglobin content when a correction for water solubility was made. Since the ghosts had frac13 the attraction of the intact cell, penetration is required to account for the distribution in the intact cell. Red cell ghost concentrates when prepared under certain conditions were found to have considerable affinity for estradiol, but on the basis of their low concentration per cell could account for only a fraction of the red cell affinity instrumental for estrogen orientation, even if their behavior did not reflect a change in properties during preparation. Ghosts prepared under the mildest conditions failed to demonstrate this affinity for estradiol. Submitted on September 14, 1959

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