Increased urinary levels of the leukocyte adhesion molecules ICAM-1 and VCAM-1 in human lupus nephritis with advanced renal histological changes: preliminary findings

Abdelkareem, Mohamed; Tamimy, Hegazy Mogahed Al; Khamis, Osama A; Abdellatif, Salama S; Hussein, Mahmoud R.

doi:10.1007/s10157-010-0322-z

Cited by 60 publications

(54 citation statements)

References 33 publications

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“…In human SLE, specific genetic polymorphisms in the gene for MCP-1 are associated with the development of LN [58, 59], and urinary MCP-1 levels reflect disease activity and correlate with renal histology and SLEDAI score [60, 61], and predict disease relapse [62]. Urine VCAM-1, an adhesion molecule important in cell recruitment into tissues, is increased in mice and patients with lupus nephritis [19, 63], and correlates with proteinuria, disease activity scores [19], and histological damage [64]. Urinary levels of IP-10, a monocyte secreted chemokine that regulates T cell migration into the kidney, accurately identifies active class IV LN, and predicts response to therapy [65].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the TWEAK/Fn14 pathway attenuates renal disease in nephrotoxic serum nephritis

Xia

Campbell

Broder

et al. 2012

Clinical Immunology

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Previously it was shown that the TNF superfamily member TWEAK (TNFSF12) acts through its receptor, Fn14, to promote proinflammatory responses in kidney cells, including the production of MCP-1, RANTES, IP-10 and KC. In addition, the TWEAK/Fn14 pathway promotes mesangial cell proliferation, vascular cell activation, and renal cell death. To study the relevance of the TWEAK/Fn14 pathway in the pathogenesis of antibody-induced nephritis using the mouse model of nephrotoxic serum nephritis (NTN), we induced NTN by passive transfer of rabbit anti-glomerular antibodies into Fn14 knockout (KO) and wild type (WT) mice. Severe proteinuria as well as renal histopathology were induced in WT but not in Fn14 KO mice. Similarly, a pharmacologic approach of anti-TWEAK mAb administration into WT mice in the NTN model significantly ameliorated proteinuria and improved kidney histology. Anti-TWEAK treatment did not affect the generation of mouse anti-rabbit antibodies; however, within the kidney there was a significant decrease in glomerular immunoglobulin deposition, as well as macrophage infiltrates and tubulointerstitial fibrosis. The mechanism of action is most likely due to reductions in downstream targets of TWEAK/Fn14 signaling, including reduced renal expression of MCP-1, VCAM-1, IP-10, RANTES as well as Fn14 itself, and other molecular pathways associated with fibrosis in anti-TWEAK treated mice. Thus, TWEAK/Fn14 interactions are instrumental in the pathogenesis of nephritis in the NTN model, apparently mediating a cascade of pathologic events locally in the kidney rather than by impacting the systemic immune response. Disrupting TWEAK/Fn14 interactions may be an innovative kidney-protective approach for the treatment of lupus nephritis and other antibody-induced renal diseases.

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Section: Discussionmentioning

confidence: 99%

Inhibition of the TWEAK/Fn14 pathway attenuates renal disease in nephrotoxic serum nephritis

Xia

Campbell

Broder

et al. 2012

Clinical Immunology

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“…121 VCAM-1 plays a role in tethering leukocytes, which are drawn to sites of inflammation, to endothelial cells. 122 Urinary VCAM-1 has been shown in several studies of human disease to be strongly correlated with LN activity and severity 77,123,124 in LN. Serum levels of VCAM have previously been shown to correlate with the severity of LN, being highest in WHO Class III and IV, versus inactive or mild nephritis (WHO Class I or II), 125 and levels diminished with treatment.…”

Section: Types Of Ln Biomarkersmentioning

confidence: 99%

Biomarkers and Updates on Pediatrics Lupus Nephritis

Bennett¹,

Brunner²

2013

Rheumatic Disease Clinics of North America

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“…The histology of DPH in SLE patients is characterized by acute lupus pneumonitis, associated interstitial infiltration by mononuclear and polynuclear leukocytes, the presence of hyaline membranes, alveolar necrosis, edema, microvascular thrombi, and intima proliferation with deposits of hemosiderin phagocytosing macrophages (6). Several studies reporting histologic evaluations of skin or kidney specimens in human SLE patients showed that the interaction between complement activated leukocytes and endothelial expression of VCAM-1 and ICAM-1 on the vasculature may be important for leukocyte migration into immune complex (IC)-deposited tissue (7,8). However, the underlying mechanism of SLE-related DPH remains unclear because lung biopsy has not been performed routinely for diagnosis in patients with hemorrhagic complications, and no suitable animal model exists for recapitulating DPH.…”

mentioning

confidence: 99%

Pristane-Induced Granulocyte Recruitment Promotes Phenotypic Conversion of Macrophages and Protects against Diffuse Pulmonary Hemorrhage in Mac-1 Deficiency

Shi

Tsuboi

Furuhashi

et al. 2014

The Journal of Immunology

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Diffuse pulmonary hemorrhage (DPH) is an uncommon but critical complication of systemic lupus erythematosus. Peritoneal administration of 2,6,10,14-tetramethylpentadecane (pristane) can recapitulate a lupus-like syndrome in mice, which can develop into DPH within a few weeks, especially in C57BL/6 mice. Mac-1 (CD11b/CD18), a leukocyte adhesion molecule, is known to play a role in inflammation by regulating migration of leukocytes into injured tissue. In this study, we aimed to clarify the role of Mac-1 in pristane-induced DPH, using Mac-1−/− and wild-type (WT) mice on a C57BL/6 background. After pristane injection, Mac-1−/− mice showed reduced prevalence of DPH and attenuated peritonitis compared with WT mice. Analysis of the peritoneal lavage on days 5 and 10 after pristane treatment revealed increased numbers of eosinophils and alternatively activated macrophages, but decreased numbers of neutrophils and classically activated macrophages in Mac-1−/− mice compared with WT. Enhanced production of IL-4 and IL-13, both key mediators of macrophage polarization toward the mannose receptor+ (MMR+) phenotype, was observed in the peritoneal cavity of Mac-1−/− mice. Depletion of neutrophils and eosinophils or adoptive transfer of classically activated macrophages resulted in the exacerbation of pristane-mediated DPH in both WT and Mac-1−/− mice. Moreover, peritoneal transfer of F4/80highMMR+ alternatively activated macrophages successfully reduced the prevalence of DPH in WT mice. Collectively, Mac-1 promoted acute inflammatory responses in the peritoneal cavity and the lungs by downregulating granulocyte migration and subsequent phenotypic conversion of macrophages in a pristane-induced systemic lupus erythematosus model.

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Increased urinary levels of the leukocyte adhesion molecules ICAM-1 and VCAM-1 in human lupus nephritis with advanced renal histological changes: preliminary findings

Cited by 60 publications

References 33 publications

Inhibition of the TWEAK/Fn14 pathway attenuates renal disease in nephrotoxic serum nephritis

Inhibition of the TWEAK/Fn14 pathway attenuates renal disease in nephrotoxic serum nephritis

Biomarkers and Updates on Pediatrics Lupus Nephritis

Pristane-Induced Granulocyte Recruitment Promotes Phenotypic Conversion of Macrophages and Protects against Diffuse Pulmonary Hemorrhage in Mac-1 Deficiency

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