Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus Nephritis
Background: Vascular microthrombotic lesions in lupus nephritis with or without antiphospholipid antibodies may relate to worse renal outcomes. Whether microthrombotic lesions are a consequence of renal inflammation or independently contribute to renal damage is unclear. Our aim was to investigate t...
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doaj-bf517498ec8648a0a843926d67b126e52020-11-24T22:41:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-08-01910.3389/fimmu.2018.01948401867Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus NephritisElena Gonzalo-Gil0Carmen García-Herrero1Oscar Toldos2Alicia Usategui3Gabriel Criado4Sonia Pérez-Yagüe5Domingo F. Barber6Jose L. Pablos7Jose L. Pablos8Maria Galindo9Maria Galindo10Instituto de Investigación, Hospital 12 de Octubre, Madrid, SpainInstituto de Investigación, Hospital 12 de Octubre, Madrid, SpainServicio de Anatomía Patológica, Hospital Universitario 12 de Octubre, Madrid, SpainInstituto de Investigación, Hospital 12 de Octubre, Madrid, SpainInstituto de Investigación, Hospital 12 de Octubre, Madrid, SpainCentro Nacional de Biotecnología (CNB-CSIC), Madrid, SpainCentro Nacional de Biotecnología (CNB-CSIC), Madrid, SpainServicio de Reumatología, Hospital Universitario 12 de Octubre, Madrid, SpainUniversidad Complutense de Madrid, Madrid, SpainServicio de Reumatología, Hospital Universitario 12 de Octubre, Madrid, SpainUniversidad Complutense de Madrid, Madrid, SpainBackground: Vascular microthrombotic lesions in lupus nephritis with or without antiphospholipid antibodies may relate to worse renal outcomes. Whether microthrombotic lesions are a consequence of renal inflammation or independently contribute to renal damage is unclear. Our aim was to investigate the relationship between microthrombotic renal vascular lesions and nephritis progression in MRL/lpr mice.Methods: MRL/lpr mice were analyzed for the presence of renal microvascular, glomerular and tubulointerstitial lesions and the effect of anti-aggregation (aspirin or clopidogrel) and dexamethasone on renal clinical and pathological manifestations was evaluated. Intravascular platelet aggregates (CD41), peri- (F4/80), and intraglomerular (Mac-2) macrophage infiltration, and C3 deposition were quantified by immunohistochemistry. Renal function was assessed by measuring proteinuria, and serum levels of creatinine and albumin. Anti-dsDNA and anti-cardiolipin antibodies, and thromboxane B2 levels were quantified by ELISA.Results: Frequency of microthrombotic renal lesions in MRL/lpr mice was high and was associated with immune-mediated renal damage. Proteinuria positively correlated with glomerular macrophage infiltration and was higher in mice with proliferative glomerular lesions. All mice had detectable anti-dsDNA and anti-cardiolipin IgG, regardless the presence of microthrombosis. Proteinuria and glomerular macrophage infiltration were significantly reduced in all treatment groups. Dexamethasone and platelet anti-aggregation similarly reduced glomerular damage and inflammation, but only platelet anti-aggregation significantly reduced anti-cardiolipin antibodies, renal complement deposition and thromboxane B2 levels.Conclusions: Platelet anti-aggregation reduced renal inflammatory damage, renal complement deposition, anti-cardiolipin antibodies, and thromboxane B2 levels and in MRL/lpr mice, suggesting that platelet activation has a pathogenic effect on immune-mediated nephritis. Our results point to MRL/lpr mice with lupus nephritis as an appropriate model to analyze the potential impact of anti-thrombotic intervention on renal inflammation.https://www.frontiersin.org/article/10.3389/fimmu.2018.01948/fullmicrothrombosisinflammationlupus nephritiscomplementmacrophagesplatelets |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Elena Gonzalo-Gil Carmen García-Herrero Oscar Toldos Alicia Usategui Gabriel Criado Sonia Pérez-Yagüe Domingo F. Barber Jose L. Pablos Jose L. Pablos Maria Galindo Maria Galindo |
spellingShingle |
Elena Gonzalo-Gil Carmen García-Herrero Oscar Toldos Alicia Usategui Gabriel Criado Sonia Pérez-Yagüe Domingo F. Barber Jose L. Pablos Jose L. Pablos Maria Galindo Maria Galindo Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus Nephritis Frontiers in Immunology microthrombosis inflammation lupus nephritis complement macrophages platelets |
author_facet |
Elena Gonzalo-Gil Carmen García-Herrero Oscar Toldos Alicia Usategui Gabriel Criado Sonia Pérez-Yagüe Domingo F. Barber Jose L. Pablos Jose L. Pablos Maria Galindo Maria Galindo |
author_sort |
Elena Gonzalo-Gil |
title |
Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus Nephritis |
title_short |
Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus Nephritis |
title_full |
Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus Nephritis |
title_fullStr |
Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus Nephritis |
title_full_unstemmed |
Microthrombotic Renal Vascular Lesions Are Associated to Increased Renal Inflammatory Infiltration in Murine Lupus Nephritis |
title_sort |
microthrombotic renal vascular lesions are associated to increased renal inflammatory infiltration in murine lupus nephritis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-08-01 |
description |
Background: Vascular microthrombotic lesions in lupus nephritis with or without antiphospholipid antibodies may relate to worse renal outcomes. Whether microthrombotic lesions are a consequence of renal inflammation or independently contribute to renal damage is unclear. Our aim was to investigate the relationship between microthrombotic renal vascular lesions and nephritis progression in MRL/lpr mice.Methods: MRL/lpr mice were analyzed for the presence of renal microvascular, glomerular and tubulointerstitial lesions and the effect of anti-aggregation (aspirin or clopidogrel) and dexamethasone on renal clinical and pathological manifestations was evaluated. Intravascular platelet aggregates (CD41), peri- (F4/80), and intraglomerular (Mac-2) macrophage infiltration, and C3 deposition were quantified by immunohistochemistry. Renal function was assessed by measuring proteinuria, and serum levels of creatinine and albumin. Anti-dsDNA and anti-cardiolipin antibodies, and thromboxane B2 levels were quantified by ELISA.Results: Frequency of microthrombotic renal lesions in MRL/lpr mice was high and was associated with immune-mediated renal damage. Proteinuria positively correlated with glomerular macrophage infiltration and was higher in mice with proliferative glomerular lesions. All mice had detectable anti-dsDNA and anti-cardiolipin IgG, regardless the presence of microthrombosis. Proteinuria and glomerular macrophage infiltration were significantly reduced in all treatment groups. Dexamethasone and platelet anti-aggregation similarly reduced glomerular damage and inflammation, but only platelet anti-aggregation significantly reduced anti-cardiolipin antibodies, renal complement deposition and thromboxane B2 levels.Conclusions: Platelet anti-aggregation reduced renal inflammatory damage, renal complement deposition, anti-cardiolipin antibodies, and thromboxane B2 levels and in MRL/lpr mice, suggesting that platelet activation has a pathogenic effect on immune-mediated nephritis. Our results point to MRL/lpr mice with lupus nephritis as an appropriate model to analyze the potential impact of anti-thrombotic intervention on renal inflammation. |
topic |
microthrombosis inflammation lupus nephritis complement macrophages platelets |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.01948/full |
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