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)

Anti-myeloperoxidase autoantibodies are found in association with idiopathic necrotizing glomerulonephritis and systemic vasculitis. It is not known if their presence is an epiphenomen or an integral part of the pathogenic process. To further delineate their hypothesized pathogenicity, we studied their ability to stimulate neutrophils to damage human umbilical vein endothelial cells in vitro. Anti-myeloperoxidase antibodies from human, rabbit and mouse sources were utilized. These antibodies stimulated neutrophils to damage endothelial cells as determined by 51Cr release. The effect was dependent on priming the neutrophils with tumor necrosis factor-alpha, and further enhanced with the addition of endotoxin. The amount of endothelial cell damage was dependent on the dose of anti-myeloperoxidase, the source of the neutrophils, the concentration of TNF, and the presence of endotoxin. Under identical conditions, control antibodies did not stimulate neutrophils to damage endothelial cells. The effect was confirmed by labeling the endothelial cells with 3H-adenine which yielded the same results. These results provide further in vitro evidence that anti-myeloperoxidase autoantibodies may play a significant role in the pathogenesis of idiopathic pauci-immune glomerulonephritis and vasculitis.
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PMID:Anti-myeloperoxidase antibodies stimulate neutrophils to damage human endothelial cells. 131 24

The ability of vasculitis-associated anti-neutrophil cytoplasm antibodies (ANCA) to activate neutrophils and mediate release of radiolabel from 111Indium-labeled cultured human umbilical vein endothelial cells (HUVEC) was determined as a measure of the potential cytotoxicity of ANCA-activated neutrophils against vascular endothelium. Priming of neutrophils with low doses of phorbol 12-myristate 13-acetate (PMA) (1 ng/ml) and ionomycin (0.1 mumol/1) was required, together with pretreatment of endothelial cells with BCNU (1,3-bis-[2-chloroethyl]-1-nitrosourea; 0.26 mmol/l). Under these conditions and using a 4-hour serum-free assay system, mouse monoclonal antibodies (MAb) to the target autoantigens proteinase-3 (Pr-3) and myeloperoxidase (MPO) mediated enhanced release of 111Indium from HUVEC compared with control MAb. Human IgG Fab2 C-ANCA (recognizing Pr-3) and P-ANCA (recognizing MPO) did likewise. Preactivation of HUVEC with TNF (50 U/ml, 4 hr) enhanced the release of 111Indium from HUVEC generated by neutrophils activated with anti-Pr-3 and anti-MPO MAb. These data support the suggestion that activation of neutrophils by ANCA within the vascular lumen may contribute to endothelial cell injury.
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PMID:Autoantibodies developing to myeloperoxidase and proteinase 3 in systemic vasculitis stimulate neutrophil cytotoxicity toward cultured endothelial cells. 132 18

The roles of beta 2 integrin molecules in neutrophil accumulation and tissue injury have been examined by the use of antibodies that are reactive with human CD11b and CD18 and cross-react with the homologous epitopes on rat neutrophils. Adherence to rat pulmonary artery endothelial cells by human neutrophils and endothelial cell killing by phorbol ester-activated human neutrophils required CD11b, CD11c, and CD18. Companion adherence studies between rat neutrophils and endothelial cells revealed a requirement for both CD11b and CD18. Neither anti-CD11b nor anti-CD18 depressed in vitro responses (O2- generation and chemotactic migration) of rat neutrophils. The accumulation of neutrophils in glycogen-induced peritoneal exudates was diminished substantially in rats treated with either anti-CD18 or anti-CD11b. In oxidant-mediated acute lung injury induced by rapid intravascular infusion of cobra venom factor, treatment of rats with either anti-CD18 or anti-CD11b significantly attenuated injury as assessed by increases in vascular permeability and hemorrhage. These protective effects correlated morphologically with diminished adhesion of neutrophils to interstitial intrapulmonary capillary endothelial cells. In studies of immune complex (BSA-anti-BSA)-induced alveolitis and dermal vasculitis, anti-CD18 had protective effects at all doses of anti-BSA employed. The protective effects of anti-CD18 correlated with diminished neutrophil accumulation in tissues at lower doses of anti-BSA. Although anti-CD11b was not effective under the same experimental conditions, intratracheal administration of this antibody conveyed protection against immune complex-induced lung injury, suggesting that both CD11b and CD18 are required for the full expression of injury. The current studies also demonstrated that when surface-bound IgG immune complexes were treated with fresh rat serum, the increment in O2- and TNF alpha generated by alveolar macrophages was suppressed by anti-CD18, but not by anti-CD11b, suggesting a heretofore unrecognized role for CD18 in the O2- and TNF-alpha responses of alveolar macrophages. Thus, neutrophil beta 2 integrins play a requisite role for the full expression of complement-dependent and oxygen radical-mediated injury of the lung and dermal vasculature.
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PMID:Roles of beta 2 integrins of rat neutrophils in complement- and oxygen radical-mediated acute inflammatory injury. 134 8

Inflammatory cells like eosinophils, neutrophils or mononuclear phagocytes have long been recognized as essential components in the pathophysiology of asthma. After recruitment in situ and subsequent activation, they are considered as responsible for epithelial and submucosal bronchial alterations. However, to access to the inflammatory site, these cells have to cross the endothelial wall, suggesting so a potential implication of endothelial cells (EC) in bronchial asthma. To test this hypothesis, we studied in a first step the modulation of vascular adhesions like intercellular adhesion molecule-1 (ICAM-1) on EC: supernatants of alveolar macrophages (AM) recovered by bronchoalveolar lavage in patients exhibiting a late asthmatic reaction, induced an enhanced expression of ICAM-1 on EC preparations; increase of ICAM-1 was clearly correlated to amounts of tumor necrosis factor-alpha (TNF alpha) present in AM supernatants, as shown by inhibition experiments with anti-TNF alpha antiserum. The second way to explore the possible role of EC in asthma was the detection of autoantibodies to EC in various allergic disorders: antibodies against a 120-kD EC antigen in patients with allergic granulomatosis and angiitis, antibodies towards a 55-kD component, common to human EC and platelets in patients with severe asthma, namely characterized by their corticosteroid dependence or by aspirin-induced intolerance. So our data suggest that bronchial asthma might result from either EC activation, through the induction of surface adhesion molecules or from an autoimmune process involving EC antigens.
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PMID:Potential implication of endothelial cells in bronchial asthma. 168 72

Different concentrations (10(7), 10(5), 10(3) cfu/ml) of Candida albicans were injected intracisternally in rabbits. The highest inoculum was fatal within 14 h in all animals. In recipients of 10(5) and 10(3) cfu/ml inocula, the mean +/- SD peak cerebrospinal fluid (CSF) tumor necrosis factor-alpha (TNF alpha) concentrations were 1.6 +/- 2.42 and 0.3 +/- 0.59 ng/ml, respectively, at 6 h; the mean +/- SD CSF leukocyte and protein concentrations were 6291 +/- 6515 and 453 +/- 674 cells/mm3 (at 24 h) and 118 +/- 90 and 109 +/- 122 mg/dl (at 12 and 24 h), respectively. At 6-10 days after inoculation, a second peak of TNF alpha activity was accompanied by increased CSF inflammation. Mortality in the 10(5) and 10(3) cfu/ml inoculum groups was 56% and 22%, respectively. Fatal infection was associated with higher second CSF peak TNF alpha and leukocyte concentrations and a larger proportion of culture-positive CSF samples. Histopathology revealed hyphal invasion, vasculitis, abscesses, and acute and chronic inflammatory infiltration of meninges and brain parenchyma. This model can be useful for evaluation of the pathogenesis and therapy of central nervous system fungal infections.
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PMID:Characteristics of experimental Candida albicans infection of the central nervous system in rabbits. 185 86

Cytokines are known to alter a number of vascular tissue cell functions. The aim of this retrospective study was to determine serum cytokine levels in patients with vasculitis and to analyse the possible relation to the severity of the disease. Tumour necrosis factor alpha (TNF alpha), interleukin-1 (IL-1)beta, IL-2, interferon (IFN)- and IFN-gamma were assayed in 33 patients with polyarteritis nodosa (PAN) or Churg and Strauss angiitis (CSA), and three with Wegener granulomatosis (WG). Serum cytokine changes were observed in most patients with active disease, i.e. before treatment was started. In the majority of patients with PAN or CSA, there was a marked increase in serum IFN-alpha and IL-2 levels, while TNF-alpha and IL-beta levels were moderately elevated. Serum IFN-gamma remained undetectable in all but one of these patients. In patients with WG, serum IFN-alpha and IL-2 levels were also elevated, whereas IL-1 beta, IFN-gamma and TNF alpha levels remained within normal limits. In paired samples of patients with PAN, IFN-alpha and IL-2 levels were significantly higher before than after treatment. These preliminary data suggest that a particular pattern of cytokine changes is associated with vasculitis and that cytokines might be involved in the pathogenesis of PAN/CSA and WG. Prospective studies are warranted to determine whether cytokines could be considered for the monitoring of disease activity and therapy.
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PMID:Serum cytokine changes in systemic vasculitis. 247 51

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

Juvenile polyarteritis syndrome (JPS) is an idiopathic febrile disease in dogs. Elevated serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) have been reported in human patients with vasculitis. We investigated whether these cytokines are also elevated in serum of dogs with JPS using sensitive bioassays. Increased levels of IL-6 activity were detected in the serum of 12 acutely ill dogs, whereas the IL-6 activity decreased to low or undetectable levels during convalescence. Treatment of 5 acute JPS dogs with prednisone resulted in a rapid clinical improvement accompanied by a decrease of IL-6 activity. Withdrawal of prednisone treatment caused reappearance of clinical symptoms and high serum IL-6 activity within a few days. TNF activity could not be detected in the samples of normal dogs, convalescent JPS, or acute JPS dogs. These studies support a role for IL-6 in the pathogenesis of JPS.
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PMID:Interleukin-6 activity in dogs with juvenile polyarteritis syndrome: effect of corticosteroids. 755 74

Antineutrophil cytoplasmic autoantibodies (ANCA) have been described in sera of patients with several forms of systemic vasculitis, including Wegener's granulomatosis and microscopic polyarteritis. The two main targets of ANCA in vasculitis are proteinase 3 (PR3) and myeloperoxidase (MPO). ANCA are capable of activating neutrophils primed by tumor necrosis factor-alpha (TNF-alpha) in vitro, which may be relevant for the induction of the vascular inflammation observed in vivo. Recently, it has been suggested that engagement of Fc gamma receptor IIa (Fc gamma RIIa) on the neutrophils is involved in the activation by ANCA. In the present study, we show that activation of the neutrophil respiratory burst by anti-PR3 and anti-MPO is strongly enhanced after TNF priming and lost on removal of the Fc parts of the antibodies. Similar results were obtained when the neutrophils were activated with antibodies against known membrane antigens without major changes in the expression of the target antigens. The TNF-induced enhancement of the neutrophil activation was not observed when adherence of the cells was prevented by continuous stirring of the suspension or by the addition of CD18 antibodies before TNF exposure. Hence, our results indicate that engagement of both Fc gamma RIIa and beta 2 integrins is instrumental in neutrophil activation induced by ANCA.
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PMID:Effect of tumor necrosis factor-induced integrin activation on Fc gamma receptor II-mediated signal transduction: relevance for activation of neutrophils by anti-proteinase 3 or anti-myeloperoxidase antibodies. 757 14

We studied sera from patients with vasculitis and controls for the presence of anti-endothelial cell antibodies (AECA) and correlated these with disease type, anti-neutrophil cytoplasmic antibodies (ANCA) and anti-myeloperoxidase (MPO) antibodies. AECA were detected by a cellular ELISA on cultured human umbilical vein endothelium. AECA were found in the sera of one of 43 patients with microscopic polyarteritis (2%), five of 27 patients with Wegener's granulomatosis (19%), three of 23 patients with an idiopathic glomerulonephritis (13%), none of eight patients with rheumatoid arthritis and three of 12 patients with rheumatoid vasculitis (25%). In patients with a vasculitis AECA titres were higher in sera with a positive ANCA as compared with ANCA negative sera although the difference was not significant (P = 0.0702) and there was no correlation between AECA and anti-MPO titres (r = 0.1171 P = 0.114). AECA binding was not enhanced following upregulation of endothelial ICAM-1 and ELAM-1 by TNF alpha. This study shows that AECA occur infrequently in microscopic polyarteritis and Wegener's granulomatosis, and are not a major antibody system in these vasculitides.
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PMID:Little evidence for anti-endothelial cell antibodies in microscopic polyarteritis and Wegener's granulomatosis. 809 69


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