Linked Life Data

9845552

Source:http://linkedlifedata.com/resource/pubmed/id/9845552

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1999-2-5
pubmed:abstractText
In sickle cell anemia (SS), some red blood cells dehydrate, forming a hyperdense (HD) cell fraction (>1.114 g/mL; mean corpuscular hemoglobin concentration [MCHC], >46 g/dL) that contains many irreversibly sickled cells (ISCs), whereas other SS red blood cells dehydrate to an intermediate density (ID; 1.090 to 1.114 g/mL; MCHC, 36 to 46 g/dL). This study asks if the potassium-chloride cotransporter (K:Cl) and the calcium-dependent potassium channel [K(Ca2+)] are participants in the formation of one or both types of dense SS red blood cells. We induced sickling by exposing normal density (ND; 1.080 to 1.090 g/mL; MCHC, 32 to 36 g/dL) SS discocytes to repetitive oxygenation-deoxygenation (O-D) cycles in vitro. At physiologic Na+, K+, and Cl-, and 0.5 to 2 mmol/L Ca2+, the appearance of dense cells was time- and pH-dependent. O-D cycling at pH 7.4 in 5% CO2-equilibrated buffer generated only ID cells, whereas O-D cycling at pH 6.8 in 5% CO2-equilibrated buffer generated both ID and HD cells, the latter taking more than 8 hours to form. At 22 hours, 35% +/- 17% of the parent ND cells were recovered in the ID fraction and 18% +/- 11% in the HD fraction. Continuous deoxygenation (N2/5% CO2) at pH 6.8 generated both ID and HD cells, but many of these cells had multiple projections, clearly different from the morphology of endogenous dense cells and ISCs. Continuous oxygenation (air/5% CO2) at pH 6.8 resulted in less than 10% dense cell (ID + HD) formation. ATP depletion substantially increased HD cell formation and moderately decreased ID cell formation. HD cells formed after 22 hours of O-D cycling at pH 6.8 contained fewer F cells than did ID cells, suggesting that HD cell formation is particularly dependent on HbS polymerization. EGTA chelation of buffer Ca2+ inhibited HD but not ID cell formation, and increasing buffer Ca2+ from 0.5 to 2 mmol/L promoted HD but not ID cell formation in some SS patients. Substitution of nitrate for Cl- inhibited ID cell formation, as did inhibitors of the K:Cl cotransporter, okadaic acid, and [(dihydroindenyl) oxy]alkanoic acid (DIOA). Conversely, inhibitors of K(Ca2+), charybdotoxin and clotrimazole, inhibited HD cell formation. The combined use of K(Ca2+) and K:Cl inhibitors nearly eliminated dense cell (ID + HD cell) formation. In summary, dense cells formed by O-D cycling for 22 hours at pH 7.4 cycling are predominately the ID type, whereas dense cells formed by O-D cycling for 22 hours at pH 6.8 are both the ID and HD type, with the latter low in HbF, suggesting that HD cell formation has a greater dependency on HbS polymerization. A combination of K:Cl cotransport and the K(Ca2+) activities account for the majority of dense cells formed, and these pathways can be driven independently. We propose a model in which reversible sickling-induced K+ loss by K:Cl primarily generates ID cells and K+ loss by the K(Ca2+) channel primarily generates HD cells. These results imply that both pathways must be inhibited to completely prevent dense SS cell formation and have potential therapeutic implications.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
92
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4844-55
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9845552-Adenosine Triphosphate, pubmed-meshheading:9845552-Anemia, Sickle Cell, pubmed-meshheading:9845552-Buffers, pubmed-meshheading:9845552-Calcium, pubmed-meshheading:9845552-Carbon Dioxide, pubmed-meshheading:9845552-Carrier Proteins, pubmed-meshheading:9845552-Centrifugation, Density Gradient, pubmed-meshheading:9845552-Chlorides, pubmed-meshheading:9845552-Enzyme Inhibitors, pubmed-meshheading:9845552-Erythrocytes, pubmed-meshheading:9845552-Fetal Hemoglobin, pubmed-meshheading:9845552-Humans, pubmed-meshheading:9845552-Hydrogen-Ion Concentration, pubmed-meshheading:9845552-Ion Transport, pubmed-meshheading:9845552-Oxygen, pubmed-meshheading:9845552-Potassium, pubmed-meshheading:9845552-Specific Gravity, pubmed-meshheading:9845552-Symporters, pubmed-meshheading:9845552-Time Factors
pubmed:year
1998
pubmed:articleTitle
Two distinct pathways mediate the formation of intermediate density cells and hyperdense cells from normal density sickle red blood cells.
pubmed:affiliation
The Albert Einstein College of Medicine and Montefiore Medical Center, Bronx Comprehensive Sickle Cell Center and Division of Hematology, Bronx, NY, USA. rschwart@worldnet.att.net
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.