Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-1-3
pubmed:abstractText
Clinical and experimental data indicate that anti-neutrophil cytoplasmic autoantibodies (ANCAs) cause glomerulonephritis and vasculitis. Here we report the first evidence that complement is an important mediator of ANCA disease. Transfer of anti-myeloperoxidase (MPO) IgG into wild-type mice or anti-MPO splenocytes into immune-deficient mice caused crescentic glomerulonephritis that could be completely blocked by complement depletion. The role of specific complement activation pathways was investigated using mice with knockout of the common pathway component C5, classic and lectin binding pathway component C4, and alternative pathway component factor B. After injection of anti-MPO IgG, C4-/- mice developed disease comparable with wild-type disease; however, C5-/- and factor B-/- mice developed no disease. To substantiate a role for complement in human ANCA disease, IgG was isolated from patients with myeloperoxidase ANCA (MPO-ANCA) or proteinase 3 ANCA (PR3-ANCA) and from controls. Incubation of MPO-ANCA or PR3-ANCA IgG with human neutrophils caused release of factors that activated complement. IgG from healthy controls did not produce this effect. The findings suggest that stimulation of neutrophils by ANCA causes release of factors that activate complement via the alternative pathway, thus initiating an inflammatory amplification loop that mediates the severe necrotizing inflammation of ANCA disease.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-10081225, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-10085024, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-10857792, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-11762946, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-1184964, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-12370273, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-12547694, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-12595502, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-1313124, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-1323218, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-1327592, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-15521377, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-15685507, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-15806479, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-15829284, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-15933057, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-15972950, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-15972951, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-16023211, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-16358221, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-16424154, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-16624929, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-18688036, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-2161532, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-2683800, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-4246566, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-7955533, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-8027554, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-8877407, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-9071707, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-9127010, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-9238044, http://linkedlifedata.com/resource/pubmed/commentcorrection/17200182-9366584
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0002-9440
pubmed:author
pubmed:issnType
Print
pubmed:volume
170
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
52-64
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Alternative complement pathway in the pathogenesis of disease mediated by anti-neutrophil cytoplasmic autoantibodies.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural