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)

Substance P has been implicated as a neuronal mediator of inflammation in various inflammatory conditions. However, the exact role played by substance P in inflammatory bowel diseases or in experimental colonic vasculitis has not been clearly understood. In this study, we examined the effect of close superior mesenteric artery injection of substance P under prevailing inflammatory conditions induced by intravenous human albumin antialbumin immune complex followed by intracolonic perfusion of 2.5% formaldehyde in rats or intracolonic perfusion of 5% alcohol alone. The immune complex- and formaldehyde-treated rats showed severe microvascular changes such as microvascular plugging by red blood cells, endothelial breakage and extravasation of plasma proteins and red blood cells. The bolus injection of 10(-8) M substance P reduced extravasation of Evans blue dye by 50% and the tissue wet to dry ratio by 20% in immune complex- and formaldehyde-perfused rats. Myeloperoxidase activity was not changed. Substance P also significantly inhibited (44%) the extravasation in alcohol-perfused rats. Pretreatment of immune complex- and formaldehyde-treated rats with substance P antagonist reversed the effect of substance P. These findings suggest that the most immediate effect of substance P may be vasodilation and clearing of vascular plugs induced by immune complex and formaldehyde. This effect of substance P differs from its chronic effect, which causes vasodilation and extravasation.
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PMID:Acute effect of substance P in immunologic vasculitis in the rat colon. 172 22

Antineutrophil cytoplasmic autoantibodies (ANCA) are present in patients with systemic vasculitis with or without renal involvement. These antibodies were first seen using indirect immunofluorescence (IIF). Two types of patterns are seen on ethanol-fixed neutrophils: the cytoplasmic and the perinuclear pattern. The cytoplasmic pattern is called C-ANCA (classical or cytoplasmic ANCA) and the perinuclear, P-ANCA. Antibodies to a serine proteinase, called proteinase 3 or myeloblastin, give rise to the C-ANCA pattern, while antibodies to myeloperoxidase give rise to the P-ANCA pattern. Proteinase 3, as well as myeloperoxidase, is present in the primary granules of neutrophils, and the P-ANCA pattern is thus an artifactual staining pattern. Myeloperoxidase, which is a basic protein, redistributes during ethanol fixation from the primary granules to the negatively charged nucleus. As an alternative to the IF technique, several solid-phase assays have been developed using either 125I or enzyme-labeled secondary antibodies. Depending on the degree of purification of the antigens used, such assays may be used for screening or as a complement to the IF method. Today it is possible to directly screen for both types of ANCA using enzyme-linked immunosorbent assay (ELISA). Simultaneous screening for antiglomerular basement membrane (GBM) antibodies (Goodpasture antibodies) increases the diagnostic yield, especially in patients with renopulmonary syndromes.
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PMID:How are antineutrophil cytoplasmic autoantibodies detected? 186 72

Myeloperoxidase (MPO) is one of the major autoantigens recognized by anti-neutrophil cytoplasm antibodies. The association of this antigen with specific disease entities requires that there is a source of pure antigen present in large quantities. Further delineation of the molecular mechanisms involved in the antigen-antibody interaction requires the ability to manipulate the molecule. The expression of recombinant MPO in Chinese hamster ovary cells has produced a source of pure protein, suitable for molecular studies. We have shown that this protein is an antigen recognized by 95% of anti-MPO antibodies from patients with systemic vasculitis. This recombinant molecule will be of use in providing an additional specific solid-phase assay for these antibodies and further forms of this protein which mirror the antigenicity of native MPO more exactly may replace chemically purified antigen. It will also be of great value in studies examining the epitopes recognized by anti-MPO antibodies and in studies of immunoregulation and T cell activation.
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PMID:Neutrophil and recombinant myeloperoxidase as antigens in ANCA positive systemic vasculitis. 755 75

Antineutrophil cytoplasmic autoantibodies (ANCAs) are found in the sera of patients with systemic vasculitis and crescentic glomerulonephritis. We developed monoclonal antibodies against myeloperoxidase (MPO), which is a major perinuclear-ANCA antigen, and examined the presence of MPO in renal tissue from patients with rapidly progressive glomerulonephritis (RPGN) using these monoclonal antibodies. Myeloperoxidase was found in the glomeruli in four of five cases of perinuclear ANCA-positive RPGN, and the distribution pattern was different from that of immunoglobulin G. In perinuclear ANCA-negative crescentic glomerulonephritis, MPO also was detected in two of three cases. Myeloperoxidase was not detected in the capillary walls or mesangium in other nephropathies, such as minimal change disease, membranous nephropathy, and mesangial proliferative glomerulonephritis, or in normal controls. Myeloperoxidase activity was elevated and inversely correlated with the titer of MPO-ANCAs in the sera of perinuclear ANCA-associated RPGN. These data suggest that MPO plays an important role in the glomerular injury of RPGN.
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PMID:Significance of myeloperoxidase in rapidly progressive glomerulonephritis. 761 Dec 43

A retrospective analysis of the authors' own findings and foreign authors' data has demonstrated that neutrophilic cytoplasm antibodies (NCAs) play a definite pathogenetic role in the activation of neutrophils, a central link in the pathogenesis of vascular wall damage in necrotizing vasculitides. The clinical value of NCAs varies with their specificity. Proteinase 3 antibodies whose detection allows one to suppose Wegener's granulomatosis are of greater diagnostic value. Myeloperoxidase antibodies are revealed in various necrotizing vasculitides and promptly progressive glomerulonephritis and more infrequently in other diseases. Thus, the detection of antibodies to proteinase-3 and myeloperoxidase in the presence of appropriate clinical signs is most likely to diagnose primary necrotizing vasculitis. The changes in the levels of NCA reflect the activity of a renal processes and the progression of the whole disease.
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PMID:[Clinical and pathogenetic aspects of kidney damage associated with neutrophilic cytoplasm antibodies]. 762 83

Anti-neutrophil cytoplasm antibodies (ANCA) are strongly associated with the development of systemic vasculitis. Myeloperoxidase and proteinase-3 have been identified as targets for P-ANCA and C-ANCA, respectively. Both enzymes are released from neutrophil azurophil granules following neutrophil activation and both are highly cationic. Purified myeloperoxidase is demonstrated to bind non-convalently to endothelial cell membranes, to retain its enzymic function following binding, and to retain its antigenicity for P-ANCA. Endothelial cell-bound myeloperoxidase enhances complement-dependent cytotoxicity of some P-ANCA sere that also contain anti-endothelial cell antibodies. Studies using purified proteinase-3 show that it also can bind to endothelial cells and be recognized by C-ANCA. The interactions of myeloperoxidase and proteinase-3 with endothelial cells and ANCA may thus contribute to the development of vascular injury in patients with systemic vasculitis.
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PMID:Anti-neutrophil cytoplasm antibodies can recognize vascular endothelial cell-bound anti-neutrophil cytoplasm antibody-associated autoantigens. 791 59

Anti-neutrophil cytoplasmic autoantibodies (ANCA) specific for constituents of neutrophil primary granules were used for enzyme immunosorbent assay in patients with vasculitic syndrome and glomerulonephritis. Proteinase 3 specific ANCA (PR3-ANCA), which include most of cytoplasmic staining pattern ANCA on indirect immunofluorescence assay (IIF) using alcohol-fixed neutrophils, were useful serologic markers for diagnosis of Wegener's granulomatosis and their titers correlated with disease activity. Myeloperoxidase specific ANCA (MPO-ANCA), which include most of perinuclear staining pattern ANCA on IIF, were detected not only in patients with well recognized clinicopathologic vasculitic syndrome and glomerulonephritis, such as microscopic polyarteritis nodosa, allergic granulomatous angitis and idiopathic crescentic necrotizing glomerulonephritis but were also detected in patients with unclassified vasculitis which are difficult to assign to a distinct diagnostic category. Patients with MPO-ANCA had common clinicopathological features, such as rapidly progressive glomerulonephritic syndrome, pulmonary hemorrhage and purpura. Histologically, patients with MPO-ANCA had focal segmental necrotizing glomerulonephritis with various degrees of crescent, pulmonary alveolar hemorrhage and leukocytoclastic vasculitis induced by necrotizing capillaries. A new clinical entity, MPO-ANCA related vasculitis in vasculitic syndrome, is proposed to manage and investigate the pathogenesis of vasculitis.
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PMID:[Anti-neutrophil cytoplasmic autoantibody (ANCA) in systemic vasculitic syndrome]. 837 2

Antineutrophil cytoplasmic antibodies (ANCA) constitute a family of auto-antibodies directed against various components of the neutrophil cytoplasm. Their identification and association with vasculitis and rapidly progressive glomerulonephritis has led to considering these diseases as possible autoimmune disorders. In addition, ANCAs constitute a diagnostic tool and a guideline for therapy during follow-up. Originally identified by Davies et al. in 1982 in 8 patients who had necrotizing glomerulonephritis but no immune deposits or systemic vasculitis (1), ANCA are now regarded as a serological marker for active pauci-immune necrotizing and crescentic glomerulonephritis, either in their renal-limited form or associated with systemic vasculitis such as Wegener's granulomatosis (WG), microscopic polyangiitis (mPA), and Churg-Strauss syndrome (CSS) (2-9). The usefulness of ANCA detection for the diagnosis of these forms of vasculitis is now established but its usefulness on follow-up remains disputed (10-13). Two major ANCA antigens have already been identified. Proteinase 3 (PR3) in a serine protease of 29 kDa initially identified by Kao and producing a cytoplasmic staining pattern termed cANCA by indirect immunofluorescence (IIF) (14,15). Myeloperoxidase (MPO) is another myeloid lysosomal enzyme producing an artefactual perinuclear staining of ethanol-fixed neutrophils termed pANCA (2,16). Both are localized in the azurophilic granules of neutrophils and monocytes, are translocated to the cell surface during cell activation (17), and are able to interact directly with ANCA. Despite this common location, MPO and PR3 are associated with a broad spectrum of clinical conditions.
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PMID:The diagnostic and prognostic significance of ANCA. 890 94

The pathogenesis of vasculitis associated with anti-neutrophil cytoplasmic antibodies is not established. The anti-neutrophil cytoplasmic antibody autoanigens proteinase 3 (PR3) and elastase induce detachment and cytolysis of endothelial cells in vitro. We investigated whether PR3 and elastase trigger endothelial cell apoptosis. Primary bovine pulmonary artery endothelial cells were treated with either PR3, elastase, or myeloperoxidase (MPO) and apoptosis assessed by four different methods. By the cell death detection enzyme-linked immunosorbent assay, DNA fragmentation increased to 208 +/- 84% or 153 +/- 27% of control with 1 micrograms/ml PR3 or elastase at 24 hours. By ultraviolet light microscopy, the percentage of apoptotic cells significantly increased (P < 0.05) with 5 or 10 micrograms/ml PR3 and 25 or 50 micrograms/ml elastase at 6, 12, or 24 hours. Values at the 24-hour time point are 15.3 +/- 6.4% or 25.8 +/- 6.6% for 5 or 10 micrograms/ml PR3 and 13.9 +/- 3.6% or 20.7 +/- 1.8% for 25 or 50 micrograms/ml elastase compared with 2.2 +/- 1.2% for control. Similarly, with flow cytometry, 5 or 10 micrograms/ml PR3 and 25 or 50 micrograms/ml elastase for 6, 12, or 24 hours demonstrated increasing apoptosis in a dose- and time-dependent manner with the highest values achieved at 24 hours (23.4 +/- 4.0% and 35.6% for 5 and 10 micrograms/ml PR3 and 31.8 +/- 4.0% and 47.8% for 25 and 50 micrograms/ml elastase compared with 7.9 +/- 2.2% in control). Typical DNA laddering was apparent from 6 to 24 hours at 5 or 10 micrograms/ml PR3 and 25 or 50 micrograms/ml elastase. Myeloperoxidase did not induce cell apoptosis. Release of PR3 and elastase by activated neutrophils during acute inflammation, including anti-neutrophil cytoplasmic antibody-associated vasculitis, may result in vascular damage by endothelial cell apoptosis.
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PMID:Apoptosis of endothelial cells induced by the neutrophil serine proteases proteinase 3 and elastase. 890 51

Myeloperoxidase (MPO) is one of the main antigen targets of anti-neutrophil cytoplasmic antibodies (ANCA) in systemic vasculitides. It has been suggested that anti-MPO antibodies may recognize a single epitope on recombinant MPO. If confirmed on native MPO, this might allow specific therapeutic intervention with anti-idiotypic MoAbs to prevent antibody antigen interaction which is thought to cause activation of neutrophils and vasculitis. We searched for restriction in the epitope recognition profile in 50 patients with anti-MPO autoantibodies, using both native and recombinant MPO. Mouse monoclonals were purified and tested in competition assays. At least four epitopes were identified on native MPO using these monoclonals and only two were conserved on recombinant MPO. We found that human MPO autoantibody response was not restricted to a single epitope on native MPO, as all sera tested did not show the same profile in competitive studies with monoclonals. Furthermore, 30% of human anti-native MPO sera failed to recognize rMPO.
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PMID:Anti-native and recombinant myeloperoxidase monoclonals and human autoantibodies. 901 Feb 67


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