Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3 Pt 1
pubmed:dateCreated
1989-4-14
pubmed:abstractText
The sickle gene has remarkably pleiotropic effects. In an attempt to understand the complex pathobiology of sickle disease, we have searched for potential relationships between various cellular abnormalities. In the present studies, we treated normal erythrocytes (RBCs) with phenazine methosulfate to stimulate intracellular generation of superoxide and thereby stimulate the excessive autoxidation characteristic of sickle RBCs. In response, RBCs show a dose-dependent increase in adherence to endothelium, easily achieving the degree of abnormal adherence typical of unmanipulated sickle RBCs. This is mediated by adverse effects of oxidant on cellular hydration, as evidenced by amelioration of abnormal adhesivity if the drug's dehydrating effect is inhibited. Consistent with potential relevance of this to sickle pathobiology, the abnormal endothelial adherence of sickle RBCs can be worsened or improved by dehydrating or hydrating these cells, respectively. These data suggest an intimate relationship between three abnormalities of sickle RBCs previously thought to be unrelated (autoxidation, dehydration, and adhesivity). Although multiple mechanisms may contribute to abnormal cell-cell interactions in sickle disease, the potentiation of sickle RBC adhesivity by cellular dehydration may help explain why clinical dehydration has been identified as a precipitant of vasocclusive crisis. Insofar as abnormal adhesivity participates in the sickle vasocclusive process, these data provide further rationale for attempting to manipulate RBC hydration as a therapeutic maneuver in this disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
256
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C579-83
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Autoxidation, dehydration, and adhesivity may be related abnormalities of sickle erythrocytes.
pubmed:affiliation
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.