Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-3-16
pubmed:abstractText
Decay-accelerating factor (DAF) is a glycosylphosphatidylinositol (GPI)-anchored membrane protein that inhibits both the classical and the alternative pathways of complement activation. DAF has been studied extensively in humans under two clinical settings: when absent from the erythrocytes of paroxysmal nocturnal hemoglobinuria (PNH) patients, who suffer from complement-mediated hemolytic anemia, and in transgenic pigs expressing human DAF, which have been developed to help overcome complement-mediated hyperacute rejection in xenotransplantation. Nevertheless, the exact role of DAF in regulating complement activation in vivo on the cell surface and the species specificity of this molecule remain to be fully characterized. To address these issues, we have used gene targeting to produce mice lacking GPI-anchored DAF. We found that erythrocytes from mice deficient in GPI-anchored DAF showed no increase in spontaneous complement activation in vivo but exhibited impaired regulation of zymosan-initiated bystander and antibody-triggered classical pathway complement activation in vitro, resulting in enhanced complement deposition. Despite a high level of C3 fixation, no homologous hemolysis occurred. It is noteworthy that GPI-linked DAF knockout erythrocytes, when tested with human and guinea pig sera, were more susceptible to heterologous complement lysis than were normal erythrocytes. These results suggest that DAF is capable of regulating homologous as well as heterologous complement activation via the alternative or the classical pathway. They also indicate that DAF deficiency alone is not sufficient to cause homologous hemolysis. In contrast, when the assembly of the membrane-attack complex is not properly regulated, as in the case of heterologous complement activation or in PNH patients, impaired erythrocyte DAF activity and enhanced C3 deposition could lead to increased hemolytic reaction.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-1370313, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-1376264, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-1378280, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-1380537, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-1383332, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-1713516, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-1720702, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-2065352, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-2445886, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-2455016, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-2473800, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-2479410, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-2481641, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-2581259, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-2966205, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-4105810, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-6211481, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-6225118, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-6238120, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-6576376, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-7511675, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-7519480, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-7545711, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-7585088, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-7687624, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-7691944, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-8231891, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-8272086, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-8892654, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-9238044, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-9365707, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-9427725, http://linkedlifedata.com/resource/pubmed/commentcorrection/9892684-9558099
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
628-33
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Role of decay-accelerating factor in regulating complement activation on the erythrocyte surface as revealed by gene targeting.
pubmed:affiliation
Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
pubmed:publicationType
Journal Article