Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have conducted an immunocytochemical analysis to investigate the presence of the recently described vascular cell adhesion molecule-1 (VCAM-1) in human kidney, using the anti-VCAM-1 monoclonal antibody 1.4C3. In normal control tissue VCAM-1 was present on some (but not all) parietal epithelial cells lining Bowman's capsule. Forty-nine of fifty clinical biopsy specimens were characterised by the additional presence of VCAM-1 on proximal tubular cells. This was most marked in biopsies of patients with interstitial nephritis or systemic vasculitis with crescentic nephritis, but was also observed in biopsies with minimal change, IgA or lupus nephropathy, or from patients with diabetic nephropathy, amyloid, or gout. Proximal tubule VCAM-1 correlated significantly with the number of transferrin-receptor-positive leukocytes (r = 0.607, p less than 0.0001) in the interstitium, but not with expression of HLA-DR by tubular cells. Surprisingly, VCAM-1 was not observed on vascular endothelial cells in these biopsies, even in the presence of a marked infiltrate; this contrasts with other tissues (e.g. skin and synovium). The presence of VCAM-1 on tubular cells in the inflamed kidney indicates the potential for these cells to interact with mononuclear cells, either as accessory cells or as cytotoxic targets. The unexpected absence of VCAM-1 in renal vascular endothelial cells suggests local differences in the endothelial cells of this organ.
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PMID:Expression of VCAM-1 in the normal and diseased kidney. 172 89

Activation of the vascular endothelium is thought to be an important facet of inflammation, thrombosis, and vasculitis. Activated endothelial cells express a number of immunologically relevant surface markers not expressed by normal endothelial cells. Many of these surface antigens are thought to augment adhesion reactions and migration. Our results show that endothelial activation may play a central role in the pathogenesis of multiple sclerosis (MS). Normal human central nervous system microvessels isolated from autopsy material do not express endothelial cell activation markers, including the adhesion proteins vascular cell adhesion molecule-1 (VCAM-1) and endothelial cell leukocyte adhesion molecule-1 (E-selectin/ELAM-1). They exhibit little to no constitutive expression of immunoreactive intercellular adhesion molecule-1 (ICAM-1) or the urokinase plasminogen activator receptor. Control microvessels exhibit no major histocompatibility complex (MHC) class II antigen. MS microvessels express significant levels of MHC class II antigens, ICAM-1, VCAM-1, and urokinase plasminogen activator receptor. E-selectin was expressed by 3 of 5 MS brains tested. Histologically unaffected areas of MS brain expressed less VCAM-1, ICAM-1, and E-selectin than did microvessels from periplaque zones. However, MHC class II antigens and urokinase plasminogen activator receptor were increased in areas exhibiting little to no evidence of leukocyte infiltration. When microvessels were examined for dual expression of activation markers, we found that in periplaque areas, 50% of microvessels coexpressed HLA-DR and VCAM-1, 28% of microvessels coexpressed HLA-DR and urokinase plasminogen activator receptor, and 43% of microvessels coexpressed HLA-DR and ICAM-1.
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PMID:Expression of immunologically relevant endothelial cell activation antigens on isolated central nervous system microvessels from patients with multiple sclerosis. 750 77

The plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1), E-selectin (sE-selectin), and vascular cell adhesion molecule-1 (sVCAM-1), might reflect endothelial activation and injury and would therefore be useful markers of disease activity in vasculitis. To investigate this we measured the levels of sICAM-1, sE-selectin, and sVCAM-1 by two-site ELISAs in the plasma of patients with (a) active vasculitis (n = 16), (b) vasculitis in remission (n = 15), (c) chronic renal failure (CRF) (n = 10), and (d) normal healthy controls (n = 10). Plasma sICAM-1 levels were significantly higher in patients with active vasculitis, 323 ng/ml (193-607) compared with patients with inactive vasculitis, 199 ng/ml (131-297); P = 0.0006 and healthy controls, 188 ng/ml (138-259); P = 0.0002. Plasma sE-selectin levels were also significantly higher in the patients with active vasculitis, 45 ng/ml (15-65) compared with patients with inactive vasculitis, 25 ng/ml (15-55); P = 0.027 but not when compared with healthy controls, 35 ng/ml (20-55); P = 0.16. There was no difference in plasma sVCAM-1 levels between patients with active vasculitis, OD 0.56 (0.45-0.85) and inactive disease, OD 0.58 (0.47-0.79) (P = 0.12) or with healthy controls OD 0.49 (0.42-0.68) (P = 0.48). There were no significant differences between the plasma levels of any of the soluble adhesion molecules between patients with active vasculitis and patients with chronic failure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Circulating soluble adhesion molecules in systemic vasculitis. 752 74

Levels of soluble adhesion molecules have been shown to reflect their cell surface expression in vitro, and thus may provide a useful surrogate marker of surface expression at inflammatory sites. In patients with SLE and vasculitis, serum levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-Selection were determined by ELISA during different stages of disease activity. Levels of soluble(s) VCAM-1 correlated with disease activity in patients with SLE, being significantly higher during active compared with inactive disease (P = 0.003), and normalizing with clinical remission. By contrast, in patients with vasculitis, although sVCAM-1 levels were elevated in active disease, they fell but did not normalize in inactive disease, suggesting that treatment may be suppressing the clinical manifestations rather than targeting the underlying pathogenic mechanism. Soluble ICAM-1 and E-Selectin levels did not relfect disease activity in either SLE or vasculitis.
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PMID:Correlation of blood levels of soluble vascular cell adhesion molecule-1 with disease activity in systemic lupus erythematosus and vasculitis. 752 85

Vascular endothelial cells respond in vitro to a number of stimuli, and in particular to cytokines, by undergoing functional and morphological alterations which endow them with the capacity to promote inflammatory reactions. We studied this process of endothelial cell activation in 20 skin biopsies from 18 patients with systemic vasculitis. At sites of cutaneous inflammation, blood vessels were lined with swollen endothelial cells which expressed increased levels of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and were associated with a mononuclear cell inflammatory infiltrate. Neutrophil infiltration was only found in the presence of endothelial leucocyte adhesion molecule-1 (ELAM-1), which was expressed in 15/20 biopsies. ELAM-1 and VCAM-1 were associated with the presence of inflammatory cytokines which induce expression of these molecules in cultured endothelial cells. Endothelial activation in vivo appears to parallel that observed in vitro, and is likely to be important in determining the nature of an inflammatory response.
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PMID:Endothelial cell activation in patients with systemic vasculitis. 753 91

Fifty-nine children with acute Kawasaki disease (KD), a childhood vasculitis, were compared with 35 children with fever due to infection and 48 healthy children. Levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in the healthy children were double those found in adults. All three soluble cell adhesion molecules and von Willebrand factor (vWF) were higher in the children with KD than in the healthy children, but only sE-selectin, a marker for activated endothelial cells, and sICAM-1 were higher than in the febrile children. The high levels of vWF in KD appear to reflect the prominent acute-phase reaction. This information can help us to understand further the complex interactions between cytokines, circulating inflammatory cells and the vascular endothelium, and may lead to new therapeutic avenues in KD and other inflammatory diseases and vasculitides.
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PMID:Soluble cell adhesion molecules and von Willebrand factor in children with Kawasaki disease. 754 71

The adhesion molecules ICAM-1, VCAM-1 and E-Selectin are regulated by proinflammatory cytokines and play an important role in the binding and activation of leukocytes in inflammatory diseases. This study measured the serum concentrations of circulating adhesion molecules (cICAM-1, cVCAM-1, cE-Selectin) by sandwich ELISA in systemic vasculitis with renal involvement (Wegener's granulomatosis WG, n = 25; systemic lupus erythematosus SLE, n = 50) in comparison to chronic glomerulonephritis (n = 10), stable renal allograft function and end-stage renal disease (CAPD/hemodialysis, each n = 10). Both cICAM-1 and cVCAM-1 levels, but not cE-Selectin, were significantly increased (p < 0.001) in active WG compared to healthy controls. cICAM-1, not cVCAM-1 differed significantly between active and inactive WG. Only cVCAM-1 was significantly elevated in active/inactive SLE (p < 0.01). WG with rapidly progressive glomerulonephritis had significantly raised levels of cICAM-1 and cVCAM-1, but not cE-Selectin, compared to controls (p < 0.005). In lupus nephritis only cVCAM-1 was significantly elevated (p < 0.01). cICAM-1 and cVCAM-1 levels were significantly raised in WG patients, that were hemodialysed and in patients with hemodialysis because of different reasons when compared to controls. However, cVCAM-1 but not cICAM-1 was significantly higher in WG with HD than without HD. Patients with chronic glomerulonephritis, renal allografts or CAPD also had significantly raised cVCAM-1 concentrations. These data suggest, that levels of circulating adhesion molecules might reflect different pathophysiologic processes in systemic vasculitides and endothelial/immune activation in non-inflammatory renal diseases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of circulating adhesion molecules ICAM-1, VCAM-1 and E-selectin in Wegener's granulomatosis, systemic lupus erythematosus and chronic renal failure. 754 87

Endothelial cell activation is achieved by the rapid, protein synthesis-independent induction of a characteristic set of genes. Because of the abundance of binding sites for the transcription factor NF-kappa B in the regulatory region of the aforementioned genes, we hypothesized that this factor might play a key role. Reactive oxygen intermediates act as second messengers in the activation of NF-kappa B. We have used the antioxidant pyrrolidine dithiocarbamate to analyze the effect of NF-kappa B inhibition on TNF alpha-induced EC activation in vitro. We show that pyrrolidine dithiocarbamate strongly reduces the TNF alpha-mediated induction of E-selectin, VCAM-1, ICAM-1, PAI-1, tissue factor, IL-8 and I kappa B-alpha. We present evidence identifying NF-kappa B as a central of EC activation. Therefore, this factor may represent a prime target for therapeutic intervention in pathologic conditions associated with EC activation such as allo- and xenograft rejection, atherosclerosis, ischemic reperfusion injury and vasculitis.
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PMID:Inhibition of NF-kappa B by pyrrolidine dithiocarbamate blocks endothelial cell activation. 754 93

We compared the levels of soluble adhesion molecules E-selectin (sE-selectin), intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) alongside von Willebrand factor (vWf), CRP and rheumatoid factor in 40 patients in serum by ELISA, rheumatoid factor by sheep red blood cell agglutination and CRP by immunonephelometry. Compared to controls, increased sE-selectin was found in patients with RA (P = 0.0015), vasculitis (P < 0.0003) and SSc (P = 0.0126), whilst raised sICAM-1 was found in RA (P < 0.0003), vasculitis (P < 0.0003) and SSc (P < 0.0378). sVCAM was lower in RA than in controls (P = 0.0102), but was unchanged in vasculitis or in SSc. vWF was raised in RA (P = 0.0102), vasculitis (P < 0.0003) and SSc (P < 0.0003). In a Spearman's rank analysis of all the data, vWf correlated with sVCAM-1 and sICAM-1 (both P < 0.001), sE-selectin with sICAM-1 (P < 0.001) and sVCAM with sICAM-1 (P < 0.005). Levels of rheumatoid factor correlated with those of sE-selectin (P = 0.003) and sVCAM-1 (P = 0.012), but there were no correlations between any index and CRP. The strongest correlations within the RA group were between sICAM and sVCAM (P = 0.001), in vasculitis it was between sE-selectin and sICAM (P < 0.001), and in SSc it was between sE-selectin and sVCAM (P = 0.019). These data suggest that the differing levels of vWf, sE-selectin and sICAM-1 in the inflammatory vasculitides may be useful in establishing a role for leucocyte/endothelial adhesion in these diseases.
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PMID:Altered levels of soluble adhesion molecules in rheumatoid arthritis, vasculitis and systemic sclerosis. 758 19

We recently identified a syndrome of recurrent cutaneous eosinophilic vasculitis in three patients. These patients had in common widespread pruritic, erythematous, purpuric papules and angioedema of face and hands associated with peripheral blood eosinophilia. Eight skin biopsies from these three patients all showed necrotizing vasculitis of the small vessels of the skin, with exclusively eosinophilic infiltration and minimal or no leukocytoclasis. The disease followed a chronic course, with recurrent, itchy, swelling skin lesions and without evidence of systemic involvement over observation periods of 3, 17, and 23 years. The skin lesions responded promptly to systemic steroid treatment, but two patients required maintenance doses for control of the disease. Immunofluorescence studies showed marked deposition of the cytotoxic eosinophil granule major basic protein in the affected vessel walls. Eosinophil-active cytokine IL-5 was detected in the serum of one patient. Expression of the vascular cell adhesion molecule-1 for eosinophil adherence was detected on the endothelium of the affected vessels. Because this disease showed distinctive clinical manifestations and characteristic histopathological features, we believe it is a distinct entity and should be distinguished from other types of vasculitis.
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PMID:Eosinophilic vasculitis syndrome: recurrent cutaneous eosinophilic necrotizing vasculitis. 764 Jan 89


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