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)

Vascular smooth muscle cells (SMC) are a major cell type comprising the walls of blood vessels. We report the synthesis of granulocyte colony-stimulating factor (G-CSF) by cultured human SMC obtained from the internal mammary artery and thoracic aorta. Interleukin-1 alpha (IL-1 alpha) greatly increased in a dose-dependent manner the amount of this cytokine produced by the SMC, with tumor necrosis factor-alpha (TNF-alpha) being less effective. Newly formed G-CSF could be detected in culture supernatants within 6 hours after IL-1 alpha or TNF-alpha treatment. Northern blot analysis of SMC stimulated with IL-1 alpha and TNF-alpha showed an increase in the amount of mRNA for G-CSF as compared with control cells. Enhanced G-CSF mRNA levels were observed when SMC were treated with cycloheximide in the absence or presence of added cytokine. In vasculitis, the walls of blood vessels become inflamed as evidenced by a leucocytic infiltrate usually dominated by polymorphonuclear neutrophil leukocytes (PMNs). G-CSF is known to stimulate PMNs, and our findings raise the possibility that G-CSF made by SMC contributes to the development of vasculitis lesions.
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PMID:Human arterial smooth muscle cells synthesize granulocyte colony-stimulating factor in response to interleukin-1 alpha and tumor necrosis factor-alpha. 128 Apr 78

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

Autoimmune diseases have been studied from the perspective of an abnormal immune response in genetically vulnerable hosts. Although the immune response is responsible for the initiation of autoimmune diseases, the effectors of the disease process likely involves cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF). These polypeptides induce a wide variety of inflammatory events which contribute to the destruction of tissue and tissue remodeling in several autoimmune diseases. Blocking IL-1 with its naturally occurring receptor antagonist, the IL-1 receptor antagonist reduces the severity of disease in animal models of inflammation and autoimmune processes. Clinical studies with the IL-1 receptor antagonist will define the role for this cytokine in the pathogenesis of autoimmune diseases such as arthritis, inflammatory bowel disease, type I diabetes and vasculitis.
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PMID:Interleukin-1 and tumor necrosis factor: effector cytokines in autoimmune diseases. 132 Sep 50

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

We have compared the role of tumor necrosis factor (TNF) in the pathogenesis of analogous acute immune complex-induced lung and dermal vascular injury models in rats. Intratracheal administration of IgG anti-bovine serum albumin (BSA), followed immediately by intravenous infusion of BSA, results in acute neutrophil-mediated alveolitis. Neutralization of intrapulmonary TNF activity with anti-TNF antibodies resulted in reduced pulmonary neutrophil recruitment and marked attenuation of lung injury. Intradermal injection of IgG anti-BSA, followed by intravenous BSA, results in acute neutrophil-mediated dermal vasculitis. Neither locally nor systemically administered anti-TNF antibodies reduced dermal vascular injury as measured by local hemorrhage and vasopermeability changes. Based on morphometric analysis and measurements of myeloperoxidase in tissue extracts, anti-TNF antibodies had no effect on dermal neutrophil recruitment. Intradermal and intrapulmonary administration of physiologic concentrations of recombinant human TNF resulted in modest, dose-dependent increases in local vasopermeability accompanied by negligible neutrophil recruitment. Administration of higher concentrations of TNF resulted in increases in both local vasopermeability and neutrophil recruitment. These data suggest that while both rat pulmonary and dermal blood vessels can respond to TNF-triggered proinflammatory events, endogenous TNF plays a much greater role in acute alveolitis than in dermal vasculitis.
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PMID:Disparate roles for TNF in the pathogenesis of acute immune complex alveolitis and dermal vasculitis. 183 7

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

Interleukin 6 (IL-6) activities and tumor necrosis factor-alpha (TNF-alpha) levels in serum were determined in 25 patients with Kawasaki disease (KD), 9 with measles, 8 with anaphylactoid purpura (AP), and in healthy children. IL-6 activity in the sera was assayed by a colorimetric assay using a murine IL-6-dependent hybridoma clone, MH60. BSF-2. Serum levels of TNF-alpha were measured by a sandwich enzyme immunoassay. IL-6 activity in the sera of patients with KD and measles was seen to increase during the acute stage. However, IL-6 activity in the sera of AP patients did not increase during the active stage. IL-6 activity in the sera of KD patients correlated with serum CRP levels and the maximum platelet counts during the course of illness. Serum TNF-alpha levels in patients with KD and AP but not measles increased during the acute stage. Since the pathogenesis of KD is systemic vasculitis with severe inflammation and thrombocytosis, the combination of IL-6, which may be responsible for severe inflammation, and TNF-alpha, which may be responsible for severe vascular injury, does play an important role in acute KD.
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PMID:[Interleukin 6 activities and tumor necrosis factor-alpha levels in serum of patients with Kawasaki disease]. 206 14

This paper reviews the evidence that cytokines induce a variety of functional and structural alterations in endothelium and that cytokine-endothelial interactions play important roles in the evolution of inflammatory and immune responses. The effect of cytokines, particularly interleukin-1 and tumor necrosis factor, on leukocyte-endothelial adhesion has led to the discovery of several endothelial adhesion molecules, and the molecular and biological characteristics of these are described. Finally, the review discusses the possible contribution of cytokine-induced activation to vascular injury in such pathological processes as septic shock, the Shwartzman reaction, delayed hypersensitivity, and immune-mediated vasculitis.
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PMID:Cytokine-endothelial interactions in inflammation, immunity, and vascular injury. 210 68

Serum levels of gamma interferon (IFN-gamma) were determined by a sandwich radioimmunoassay in 45 patients with Kawasaki disease (KD), 14 with measles, 3 with streptococcal infection, 17 with anaphylactoid purpura, 6 with various vasculitis and also in 10 healthy children. Serum levels of IFN-gamma were seen to increase during the acute phase of KD and measles. In addition, serum levels of tumor necrosis factor (TNF) and interleukin 2 receptor (IL-2R) were measured simultaneously in 45 patients with KD. In KD patients with coronary-artery lesions (CAL), the percentage of positive cases for TNF (greater than or equal to 10 units/ml), IL-2R (greater than or equal to 1056 units/ml) and IFN-gamma (greater than or equal to 0.3 units/ml) was higher than that in patients without CAL. Several cytokines in association with activated monocytes/macrophages and T lymphocytes were detected in the serum during acute KD. These results suggest that aggressive activation of immuno-competent cells develops in KD involved CAL.
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PMID:[Serum gamma interferon levels in relation to tumor necrosis factor and interleukin 2 receptor in patients with Kawasaki disease involving coronary-artery lesions]. 211 9

Anti-neutrophil cytoplasmic autoantibodies (ANCA) are in the circulation of most patients with pauci-immune necrotizing vasculitis and pauci-immune crescentic glomerulonephritis. The current study demonstrates an effect of these autoantibodies on neutrophil function in vitro. ANCA cause normal human neutrophils to undergo an oxidative burst and degranulate. Both ANCA phenotypes (i.e., cytoplasmic-pattern ANCA and myeloperoxidase-specific ANCA) induce neutrophil activation. ANCA sera and purified immunoglobulins significantly increase the release of reactive oxygen species when compared with controls. ANCA, in a dose-dependent manner, induce the release of primary granule contents. These effects are markedly enhanced by priming neutrophils with tumor necrosis factor. Flow cytometry studies demonstrate the presence of myeloperoxidase on the surface of neutrophils after cytokine priming, indicating that primed neutrophils have ANCA antigens at their surfaces to interact with ANCA. These observations suggest an in vivo pathogenetic role for ANCA. We propose that, in patients with necrotizing vasculitis, ANCA-induced release of toxic oxygen radicals and noxious granule enzymes from cytokine-primed neutrophils could be mediating vascular inflammation.
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PMID:Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. 216 32


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