File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Intrinsic renal cell and leukocyte-derived TLR4 aggravate experimental anti-MPO glomerulonephritis

TitleIntrinsic renal cell and leukocyte-derived TLR4 aggravate experimental anti-MPO glomerulonephritis
Authors
Keywordsanti-MPO antibody
chemokine
endothelial cell
neutrophil
Issue Date2010
Citation
Kidney International, 2010, v. 78 n. 12, p. 1263-1274 How to Cite?
AbstractAntimyeloperoxidase antibodies can cause crescentic glomerulonephritis and pulmonary hemorrhage. Toll-like receptors (TLRs) respond to infectious agents activating host defenses, whereas infections potentially initiate disease and provoke relapses. Neutrophils were found to be key effector cells of injury in experimental models, as disease does not occur in their absence and injury is enhanced by lipopolysaccharide (LPS). In this study, highly purified LPS (a pure TLR4 ligand) acted with antimyeloperoxidase antibodies to synergistically increase kidney and lung neutrophil recruitment and functional injury; effects abrogated in TLR4-deficient mice. Increased kidney TLR4 expression after stimulation predominantly occurred in glomerular endothelial cells. Enhanced glomerular neutrophil recruitment correlated with increased kidney mRNA expression of CXCL1 and CXCL2 (homologs of human CXCL8), whereas their preemptive neutralization decreased neutrophil recruitment. Disease induction in bone marrow chimeric mice showed that TLR4 in both bone marrow and renal parenchymal cells is required for maximal neutrophil recruitment and glomerular injury. Further studies in human glomerular cell lines stimulated with LPS found that glomerular endothelial cells were the prominent sources of CXCL8. Thus, our results define a role for TLR4 expression in bone marrow-derived and glomerular endothelial cells in neutrophil recruitment and subsequent functional and histological renal injury in experimental antimyeloperoxidase glomerulonephritis. © 2010 International Society of Nephrology.
Persistent Identifierhttp://hdl.handle.net/10722/195492
ISSN
2023 Impact Factor: 14.8
2023 SCImago Journal Rankings: 3.886
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSummers, SA-
dc.contributor.authorVan Der Veen, BS-
dc.contributor.authorO'Sullivan, KM-
dc.contributor.authorGan, P-Y-
dc.contributor.authorOoi, JD-
dc.contributor.authorHeeringa, P-
dc.contributor.authorSatchell, SC-
dc.contributor.authorMathieson, PW-
dc.contributor.authorSaleem, MA-
dc.contributor.authorVisvanathan, K-
dc.contributor.authorHoldsworth, SR-
dc.contributor.authorKitching, AR-
dc.date.accessioned2014-02-28T06:12:14Z-
dc.date.available2014-02-28T06:12:14Z-
dc.date.issued2010-
dc.identifier.citationKidney International, 2010, v. 78 n. 12, p. 1263-1274-
dc.identifier.issn0085-2538-
dc.identifier.urihttp://hdl.handle.net/10722/195492-
dc.description.abstractAntimyeloperoxidase antibodies can cause crescentic glomerulonephritis and pulmonary hemorrhage. Toll-like receptors (TLRs) respond to infectious agents activating host defenses, whereas infections potentially initiate disease and provoke relapses. Neutrophils were found to be key effector cells of injury in experimental models, as disease does not occur in their absence and injury is enhanced by lipopolysaccharide (LPS). In this study, highly purified LPS (a pure TLR4 ligand) acted with antimyeloperoxidase antibodies to synergistically increase kidney and lung neutrophil recruitment and functional injury; effects abrogated in TLR4-deficient mice. Increased kidney TLR4 expression after stimulation predominantly occurred in glomerular endothelial cells. Enhanced glomerular neutrophil recruitment correlated with increased kidney mRNA expression of CXCL1 and CXCL2 (homologs of human CXCL8), whereas their preemptive neutralization decreased neutrophil recruitment. Disease induction in bone marrow chimeric mice showed that TLR4 in both bone marrow and renal parenchymal cells is required for maximal neutrophil recruitment and glomerular injury. Further studies in human glomerular cell lines stimulated with LPS found that glomerular endothelial cells were the prominent sources of CXCL8. Thus, our results define a role for TLR4 expression in bone marrow-derived and glomerular endothelial cells in neutrophil recruitment and subsequent functional and histological renal injury in experimental antimyeloperoxidase glomerulonephritis. © 2010 International Society of Nephrology.-
dc.languageeng-
dc.relation.ispartofKidney International-
dc.subjectanti-MPO antibody-
dc.subjectchemokine-
dc.subjectendothelial cell-
dc.subjectneutrophil-
dc.titleIntrinsic renal cell and leukocyte-derived TLR4 aggravate experimental anti-MPO glomerulonephritis-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1038/ki.2010.327-
dc.identifier.pmid20844472-
dc.identifier.scopuseid_2-s2.0-78649667341-
dc.identifier.volume78-
dc.identifier.issue12-
dc.identifier.spage1263-
dc.identifier.epage1274-
dc.identifier.isiWOS:000284752900010-
dc.identifier.issnl0085-2538-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats