Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Flaxseed is rich in alpha-linolenic acid (alpha-LA) which has anti-atherogenic properties, and lignans which are platelet activating factor (PAF)-receptor antagonists. These constituents of flaxseed, and its beneficial effects in the MRL/lpr lupus mouse prompted us to perform this dosing study in lupus nephritis patients. Nine patients were enrolled, eight of whom completed the study. After the baseline studies, patients were given 15, 30, and 45 g of flaxseed/day sequentially at four week intervals, followed by a five-week washout period. Compliance, disease activity, blood pressure, plasma lipids, rheology, PAF-induced platelet aggregation, renal function, and serum immunology were assessed. Flaxseed-sachet count and a significant increase of serum alpha-LA indicated good compliance for 15 and 30 g doses. Total and LDL cholesterol, and blood viscosity were significantly reduced with 30 g and to a lesser extent 45 g doses. PAF-induced platelet aggregation was inhibited by all doses. There was a significant decline in serum creatinine with 30 and 45 g, and a concomitant increase in creatinine clearance with increasing flaxseed dose. Proteinuria was reduced with 30 g and to a lesser extent with 45 g of flaxseed. Complement C3 was significantly elevated by all three doses. CD11b expression on neutrophils, a measure of C3bi receptors, was significantly reduced with the 30 g dose. In conclusion, 30 g flaxseed/day was well tolerated and conferred benefit in terms of renal function as well as inflammatory and atherogenic mechanisms important in the pathogenesis of lupus nephritis.
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PMID:Flaxseed: a potential treatment for lupus nephritis. 756 15

Requirements for leukocyte adhesion molecules as well as cytokines have been determined in the rat model of acute nephrotoxic nephritis. Proteinuria (at 24 h) and neutrophil accumulation in renal glomeruli (at 6 h) have been used as the endpoints. For full accumulation in glomeruli of neutrophils as well as full development of proteinuria, requirements have been demonstrated for TNF alpha, (but not IL-1), CD11b (but not CD11a), very late arising-4 (CD49d/CD29), and intercellular adhesion molecule-1 but not endothelial leukocyte adhesion molecule-1 (E-selectin). By immunohistochemical approaches, infusion of antibody to glomerular basement membrane induced glomerular upregulation of intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, and vascular adhesion molecule-1. Treatment of rats with anti-TNF alpha or soluble recombinant human TNF receptor-1 blocked this expression. Renal arterial infusion of TNF alpha induced glomerular expression of all three endothelial adhesion molecules, but infusion of IL-1 beta did not. These data suggest that, in neutrophil and complement-dependent anti-glomerular basement membrane-induced acute nephritis in rats, there are selective requirements for cytokines, beta 1 and beta 2 integrins, and endothelial adhesion molecules. These requirements contrast with those found in other vascular beds in which complement and neutrophil-induced vascular injury has been induced by deposition of immune complexes.
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PMID:Requirements for leukocyte adhesion molecules in nephrotoxic nephritis. 767 12

Intraglomerular expression of complement receptors (CR) was investigated chronologically in 22 repeatedly biopsied patients with membranoproliferative glomerulonephritis (MPGN) type I by indirect immunoperoxidase staining using MoAbs. Patients were divided into two groups based on whether intraglomerular C3c deposition was decreased at the second biopsy (2nd Bx) (group A, n = 12), or not (group B, n = 10). At the first biopsy (1st Bx), the severity of glomerular injury and the degree of glomerular C3c deposition were compatible between the two groups. Four patterns of CR1 (CD35) expression on podocytes were recognized: normal; generally decreased; focally/segmentally lost; and completely lost. The numbers of CR3 (CD11b/CD18)- and CR4 (CD11c/CD18)-positive cells per glomerular cross-section were counted. At the 1st Bx, no significant difference was found in the number of CR3+ or CR4+ cells between the two groups. At the 2nd Bx, the numbers of both the CR3+ and CR4+ cells were significantly decreased only in group A (P < 0.01). The numbers of CR3+ and CR4+ cells were significantly higher in cases with moderate or marked C3c deposits than in those with no or mild C3c deposits. The intensity of CR1 expression in group B was less than that in group A at both the 1st and 2nd Bx (1st, P < 0.05; 2nd, P < 0.01), and chronological improvement of CR1 expression was observed only in group A. The severity of glomerular injury was increased only in group B (P < 0.01), and was associated with persistent massive proteinuria and hypocomplementaemia. Our results suggest that, in cases with an adverse outcome, a more severe defect of CR1 initially exists and the expression of CR1 is not recoverable chronologically. This irreversible decrease or loss of CR1 may partly contribute to the continuous C3c deposition and intraglomerular infiltration of CR3+ and CR4+ cells.
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PMID:Participation of CR1 (CD35), CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in membranoproliferative glomerulonephritis type I. 774 66

Nephrotoxic nephritis (NTN), a model of autoimmune glomerulonephritis, is characterized by glomerular inflammation, which results in both proteinuria and an increase in eicosanoid production. In light of the ability of CD18 integrins to participate in leukocyte adherence (and thereby migration), we examined the role of the integrin CD11b/CD18 in NTN using OX42, a monoclonal antibody directed against rat CD11b. Administration of OX42 30 min before induction of NTN decreased proteinuria (by 50%) but did not affect the number of leukocytes found in the glomerulus or the accompanying increase in glomerular eicosanoid production. Administration of OX42 16 h before disease induction led to a more substantial decrease in proteinuria (80%) and, in contrast to 30 min pretreatment, decreased the number of neutrophils found in the glomerulus and the accompanying increase in glomerular eicosanoid production (both by 50%). OX42 pretreatment had no effect on the number of macrophages found in glomeruli. Circulating leukocytes from animals treated with OX42 in vivo showed saturating surface levels of antibody by fluorescence-activated cell sorting (FACS) analysis and normal upregulation of CD11b by pharmacological activation. Sixteen hours after in vivo injection of OX42, 50% more peripheral leukocytes were labeled relative to control leukocytes labeled with OX42 ex vivo. Glomerular leukocytes in NTN exhibited upregulated expression of CD11b relative to peripheral leukocytes. These data show that CD11b/CD18 may participate in the acute expression of glomerular damage in NTN in a fashion not wholly dependent on blocking neutrophil migration into glomeruli. Blockade of surface receptors (as opposed to inhibition of upregulation) is sufficient to obtain this effect.
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PMID:Attenuation of immune-mediated glomerulonephritis with an anti-CD11b monoclonal antibody. 809 79

We studied the expression of adhesion molecules on infiltrating leukocytes and tubular cells in chronic tubulointerstitial nephritis associated with puromycin aminonucleoside (PA) nephrosis. Rats received injections of PA (2 mg/100 g body wt) weekly for the first 3 weeks and every other week thereafter. Rats were killed at 0, 3, 5, 8, and 12 weeks after the start of injections. From the third to the fifth week, the initial infiltrating cells in interstitial tissue were mainly CD4+ T lymphocytes. At the fifth week, ICAM-1, CD44, and hyaluronate were expressed on infiltrating cells in interstitial tissue. At the eighth week, the number of infiltrating cells reached a peak and consisted of T lymphocytes (CD4, CD8) and macrophages (ED1, MHC class II, CD11b, and CD18). The severity of interstitial infiltration was correlated with the degree of proteinuria and with ICAM-1 expression. Our results suggest that CD4+ T lymphocytes may contribute to the production of initial tubular injury. Expression of ICAM-1 helps mononuclear cells migrate to the interstitium. In addition, expression of CD44 and hyaluronate may play important roles in the chronicity of tubulointerstitial nephritis.
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PMID:The relationship of adhesion molecules and leukocyte infiltration in chronic tubulointerstitial nephritis induced by puromycin aminonucleoside in Wistar rats. 863 80

Glomerular expression of intercellular adhesion molecule-1 (ICAM1) (CD54) and membrane cofactor protein (MCP; CD46) and positive infiltrating cells in leukocyte function associated antigen-1 (LFA1)alpha (CD11a) and C3bi receptors (CR3/CD11b, CR4/CD11c) were examined by the indirect immunoperoxidase method on 43 sets of repeated renal biopsy specimens from patients with immunoglobulin A nephropathy. Twenty-four-hour urine protein at the time of renal biopsy was also evaluated. Glomerular infiltration of LFA1alpha+ cells was significantly correlated with glomerular expression of ICAM1 (r = 0.494, P < 0.0001). Glomerular complement receptor type 4 (CR4)+ cells were significantly correlated with glomerular expression of MCP (r = 0.405, P < 0.0001). The glomerular expressions of ICAM1 and MCP were significantly correlated with each other (r = 0.700, P < 0.00001). The glomerular infiltrations of LFA1alpha+ and CR4+ cells were highly correlated with each other (r = 0.884, P < 0.00001), and both cell types were significantly correlated with urine protein (respectively, r = 0.426 and 0.478, P < 0.001 and 0.0001). When the change in these parameters between the time of the initial and follow-up biopsies was evaluated, there was a significant correlation between the change in glomerular expression of ICAM1 (DeltaICAM1) and MCP (DeltaMCP) as well as between the change in glomerular infiltration of LFA1alpha+ cells (DeltaLFA1alpha+) and CR4+ cells (DeltaCR4+). Both DeltaLFA1alpha+ and DeltaCR4+ were significantly correlated with the change in urine protein. These findings suggest that ICAM1/LFA1 interaction and MCP-mediated C3bi/C3biR interaction cooperate and participate in persistent glomerular infiltration of immune cells in immunoglobulin A nephropathy, and that these LFA1alpha+ and C3biR+ cells contribute to the induction of proteinuria.
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PMID:Intercellular adhesion molecule-1/leukocyte function associated antigen-1-mediated and complement receptor type 4-mediated infiltration and activation of glomerular immune cells in immunoglobulin A nephropathy. 871 20

Intercellular adhesion molecule-1 (ICAM-1, CD54), an adhesion molecule of the immunoglobulin superfamily, is an endothelial cell surface ligand for such leukocyte integrins as lymphocyte-function-associated molecule 1 (LFA-1, CD11a/CD18), Mac-1 (CD11b/CD18) and CD43. These molecules mediate adhesive interactions between leukocytes and endothelial cells and are critically involved in infiltration of leukocytes into inflammatory lesions. We examined the expression of ICAM-1 in renal tissues of Masugi nephritis rats and directly examined the role of ICAM-1 by administration of neutralizing monoclonal antibodies (MAbs) to rat ICAM-1, LFA-1 alpha-subunit (LFA-1 alpha), beta-subunit (LFA-1 beta) and Mac-1 alpha-subunit (Mac-1 alpha). Within 3 h after injection of nephrotoxic serum, increased expression of ICAM-1 was detected in the glomeruli by in situ hybridization and an immunofluorescence study. Proteinuria was significantly suppressed by the MAbs against ICAM-1, Mac-1 alpha and LFA-1 beta. Neutrophil infiltration into the glomeruli was significantly prevented by injection of the MAbs against ICAM-1, LFA-1 alpha and LFA-1 beta. These results indicate that both ICAM-1/LFA-1 and ICAM-1/Mac-1 pathways are involved in neutrophil infiltration into the glomeruli. On the other hand, monocytic infiltration was prevented by the MAbs against ICAM-1, LFA-1 alpha and LFA-1 beta but not by anti-Mac-1 alpha MAb. Due to these results, ICAM-1 is considered to be a critical molecule involved in the pathogenesis of the leukocyte infiltration into the glomeruli in the heterologous phase of Masugi nephritis. Anti-ICAM-1 antibody may be beneficial in the treatment of leukocyte-mediated glomerular diseases.
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PMID:The critical role of intercellular adhesion molecule-1 in Masugi nephritis in rats. 877 54

Glomerular deposits of fibrin-related antigens (FRA), C3c, membrane attack complex (MAC) were examined by the immunoperoxidase method on 176 renal biopsy specimens from 120 cases with IgA nephropathy including 56 cases with sequential biopsies. On 47 sets of repeated renal biopsy specimens, the glomerular infiltration of the following immune cells was examined by the indirect immunoperoxidase method; immune cells positive for C3bi receptor (C3biR; CR3/CD11b, CR4/CD11c), HLADR antigen and several leukocyte surface markers (CD45R, CD3, CD15 and CD68). Twenty-four-hour urine protein (UP) at the renal biopsy was also evaluated. The glomerular deposition of FRA was inversely correlated with C3c/MAC deposition (p < 0.00001). Most cases (163 of 176) were classified into the following two types; type C with dominant deposition of C3c (97 cases) and type F with dominant deposition of FRA (66 cases), except for 13 cases with equivalent deposits of C3c and FRA (7 cases, type B) and without C3 or FRA deposits (6 cases, type O). In 56 rebiopsied cases, apparent conversion from type F or C into the other was observed only in one case though a few cases in type C lost or reduced C3c deposition to an equivocal type at the follow-up biopsy, which were included in type C', an expanded category of type C. In the whole cases, the glomerular infiltration of immune cells was significantly correlated with FRA deposition (p < 0.0002) but not with C3c. Glomerular CD11c+ cells were significantly correlated with C3c deposition in type C' (p < 0.0001), but not in type F. Glomerular HLADR positive immune cells were significantly correlated with glomerular CD3+ T cells in type F (p < 0.001), but not in type C'. In type C', UP was significantly correlated with glomerular CD11c+ cells (p < 0.0001) but not with CD 15+ or HLADR+ cells. On the other hand, in type F, UP was significantly correlated with CD 15+ and HLADR+ cells (p < 0.001) but not with CD11c+ cells. These results suggested that there are multiple pathways in inducing glomerular infiltration of immune cells in IgA nephropathy. In type C, local activation of complements might primarily induce immune cell infiltration through C3biR and these C3biR+ cells are involved in inducing proteinuria. On the other hand, in type F, in which complement activation is weak, immune cells might infiltrate directly through their Fc receptor or MHC class II antigens, and might be activated by T-cell/macrophage interaction to induce proteinuria.
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PMID:Mechanism of infiltration and activation of glomerular monocytes/macrophages in IgA nephropathy. 909 44

The expression of intercellular adhesion molecule-1 (ICAM-1), the ligand leucocyte function antigen-1 (LFA-1, CD11a), and complement receptor type 3 (CR3, or Mac-1, CD11b) has been studied in murine kidneys acutely infected with the fatal malaria parasite Plasmodium berghei ANKA. Thirty-six kidney sections from five groups of C57BL/6J mice on day 5, 10, 15, and 20 post-infection, and normal controls, were stained with monoclonal antibodies against ICAM-1, LFA-1, and Mac-1. There was markedly enhanced expression of ICAM-1 in the glomerular mesangium and the endothelium of blood vessels from day 10 post-infection. ICAM-1 was also found in the proximal tubular epithelial cells in an apical location, with a linear pattern. In addition, the glomeruli showed positive staining for LFA-1 and Mac-1 on day 10 post-infection, mainly in the infiltrating inflammatory cells. Mesangial cells and inflammatory cells in the cortical tubulointerstitium showed positive staining for ICAM-1, LFA-1, and Mac-1 at the later stages of infection. There were strong correlations between ICAM-1 expression on endothelial cells of glomerular/peritubular capillaries with inflammatory cells positive for LFA-1 and Mac-1, which correlated with proteinuria. These findings show that several adhesion molecules are up-regulated in murine malaria-associated nephritis. The expression of ICAM-1 on endothelial cells correlated with the severity of inflammatory responses, indicating the relationship between the expression of adhesion molecules and cell-mediated immune renal injury. It is suggested that adhesion molecules play an important role in the pathogenesis of murine nephritis. Better knowledge of the function of these molecules in malaria infection may open new approaches to antimalarial therapy.
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PMID:In situ analysis of adhesion molecule expression in kidneys infected with murine malaria. 971 51

Peripheral blood leukocytes infiltrate the kidney in chronic serum sickness (CSS). We therefore studied the expression of CD54 and its ligands CD18 and CD11b/c in CSS in 10 rats with CSS, 6 rats immunized similarly who did not developed proteinuria (no-CSS group), and 10 normal rats (control group). Intense (6 to 35 times more than controls) leukocyte infiltration was observed in CSS. The CSS group over-expressed CD54 in glomeruli and interstitium in association with increments in CD18- and CD11b/c-positive cells ranging 2.5 to 7 times the number found in controls. 75% of infiltrating leukocytes expressed CD18 and 87% expressed CD11b/c. The non-CSS group had leukocyte infiltration and expression of adhesion molecules similar to control group. Adherence of CD43-positive cells to renal tissues was 4 times higher in renal tissue from CSS rats than to normal kidney. Pretreatment with corresponding Mabs reduced adherence by half. We concluded that over-expression of CD54 and its ligands CD18 and CD11b/c in infiltrating leukocytes occur in CSS. Binding experiments suggest the functional relevance of these molecules.
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PMID:Expression of adhesion molecules in chronic serum sickness in rats. 1008 Aug 31


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