Linked Life Data

8007582

Source:http://linkedlifedata.com/resource/pubmed/id/8007582

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1994-7-18
pubmed:abstractText
The mechanisms underlying glomerular capillary wall injury in Wegener's granulomatosis (WG) are not well understood. Anti-neutrophil cytoplasmic antibodies (ANCA), present in sera from patients with WG, are known to stimulate respiratory burst and degranulation of primed polymorphonuclear neutrophils (PMN) in vitro. Experimental studies have shown that oxygen radical production and lysosomal enzymes are important mediators of glomerular capillary wall injury. In the present study we investigated the presence of activated PMN and the extracellular localization of lysosomal enzymes in 28 consecutive renal biopsies from patients with WG. The presence of activated PMN within the renal biopsies was compared with the capacity of ANCA, isolated from simultaneously drawn serum samples, to activate primed PMN obtained from a normal donor. Both parameters were also related to renal function. Renal biopsies were obtained from newly diagnosed WG patients before therapy had started. Activation of PMN in the biopsies was assessed by measuring hydrogen peroxide production in situ. The number of activated PMN in the biopsy correlated with the extent of impairment of renal function. Proteinase 3, myeloperoxidase, and elastase, all targets of ANCA, were localized extracellularly in renal tissue and were also found within tubular epithelial cells. All ANCA positive samples were capable of activating primed PMN. The amount of activation correlated with the ANCA titer in those samples. No correlation, however, was found between the in vitro capacity of ANCA-positive IgG fractions to activate primed PMN and the number of activated PMN present in the renal biopsy. We conclude that activated PMN producing toxic oxygen metabolites and releasing lysosomal enzymes, are present in renal biopsies from patients with WG. The amount of activated PMN present within the kidney, and not the capacity of the corresponding ANCA to activate PMN, correlates with renal tissue damage as assessed by serum creatinine levels.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Antineutrophil..., http://linkedlifedata.com/resource/pubmed/chemical/Autoantibodies, http://linkedlifedata.com/resource/pubmed/chemical/Autoantigens, http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers, http://linkedlifedata.com/resource/pubmed/chemical/Complement System Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G, http://linkedlifedata.com/resource/pubmed/chemical/Myeloblastin, http://linkedlifedata.com/resource/pubmed/chemical/Pancreatic Elastase, http://linkedlifedata.com/resource/pubmed/chemical/Peroxidase, http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species, http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Superoxides
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0085-2538
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1120-31
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Neutrophil activation in vitro and in vivo in Wegener's granulomatosis.
pubmed:affiliation
Department of Clinical Immunology, University of Groningen, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't