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- Publisher Website: 10.1016/j.kint.2015.11.024
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- PMID: 26924054
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Article: Complement receptor 3 mediates renal protection in experimental C3 glomerulopathy
Title | Complement receptor 3 mediates renal protection in experimental C3 glomerulopathy |
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Authors | |
Keywords | glomerulonephritis macrophages complement |
Issue Date | 2016 |
Citation | Kidney International, 2016, v. 89, n. 4, p. 823-832 How to Cite? |
Abstract | © 2016 International Society of Nephrology. C3 glomerulopathy is a complement-mediated renal disease that is frequently associated with abnormalities in regulation of the complement alternative pathway. Mice with deficiency of factor H (Cfh-/-), a negative alternative pathway regulator, are an established experimental model of C3 glomerulopathy in which complement C3 fragments including iC3b accumulate along the glomerular basement membrane. Here we show that deficiency of complement receptor 3 (CR3), the main receptor for iC3b, enhances the severity of spontaneous renal disease in Cfh-/- mice. This effect was found to be dependent on CR3 expression on bone marrow-derived cells. CR3 also mediated renal protection outside the setting of factor H deficiency, as shown by the development of enhanced renal injury in CR3-deficient mice during accelerated nephrotoxic nephritis. The iC3b-CR3 interaction downregulated the proinflammatory cytokine response of both murine and human macrophages to lipopolysaccharide stimulation in vitro, suggesting that the protective effect of CR3 on glomerular injury was mediated via modulation of macrophage-derived proinflammatory cytokines. Thus, CR3 has a protective role in glomerulonephritis and suggests that pharmacologic potentiation of the macrophage CR3 interaction with iC3b could be therapeutically beneficial. |
Persistent Identifier | http://hdl.handle.net/10722/279673 |
ISSN | 2023 Impact Factor: 14.8 2023 SCImago Journal Rankings: 3.886 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Barbour, Thomas D. | - |
dc.contributor.author | Ling, Guang Sheng | - |
dc.contributor.author | Ruseva, Marieta M. | - |
dc.contributor.author | Fossati-Jimack, Liliane | - |
dc.contributor.author | Cook, H. Terence | - |
dc.contributor.author | Botto, Marina | - |
dc.contributor.author | Pickering, Matthew C. | - |
dc.date.accessioned | 2019-11-27T08:09:44Z | - |
dc.date.available | 2019-11-27T08:09:44Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | Kidney International, 2016, v. 89, n. 4, p. 823-832 | - |
dc.identifier.issn | 0085-2538 | - |
dc.identifier.uri | http://hdl.handle.net/10722/279673 | - |
dc.description.abstract | © 2016 International Society of Nephrology. C3 glomerulopathy is a complement-mediated renal disease that is frequently associated with abnormalities in regulation of the complement alternative pathway. Mice with deficiency of factor H (Cfh-/-), a negative alternative pathway regulator, are an established experimental model of C3 glomerulopathy in which complement C3 fragments including iC3b accumulate along the glomerular basement membrane. Here we show that deficiency of complement receptor 3 (CR3), the main receptor for iC3b, enhances the severity of spontaneous renal disease in Cfh-/- mice. This effect was found to be dependent on CR3 expression on bone marrow-derived cells. CR3 also mediated renal protection outside the setting of factor H deficiency, as shown by the development of enhanced renal injury in CR3-deficient mice during accelerated nephrotoxic nephritis. The iC3b-CR3 interaction downregulated the proinflammatory cytokine response of both murine and human macrophages to lipopolysaccharide stimulation in vitro, suggesting that the protective effect of CR3 on glomerular injury was mediated via modulation of macrophage-derived proinflammatory cytokines. Thus, CR3 has a protective role in glomerulonephritis and suggests that pharmacologic potentiation of the macrophage CR3 interaction with iC3b could be therapeutically beneficial. | - |
dc.language | eng | - |
dc.relation.ispartof | Kidney International | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | glomerulonephritis | - |
dc.subject | macrophages | - |
dc.subject | complement | - |
dc.title | Complement receptor 3 mediates renal protection in experimental C3 glomerulopathy | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1016/j.kint.2015.11.024 | - |
dc.identifier.pmid | 26924054 | - |
dc.identifier.scopus | eid_2-s2.0-84964607356 | - |
dc.identifier.volume | 89 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 823 | - |
dc.identifier.epage | 832 | - |
dc.identifier.eissn | 1523-1755 | - |
dc.identifier.isi | WOS:000372521100014 | - |
dc.identifier.issnl | 0085-2538 | - |