Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using a specific substrate, no leucocyte elastase activity could be detected in 55 synovial fluids, including 29 from patients with rheumatoid arthritis (RA). However, a high percentage of samples contained phagocytic inclusions of elastase, alpha 1-proteinase inhibitor (alpha 1-PI) and alpha 2-macroglobulin (alpha 2-MG) in both the polymorphonuclear (PMN) and mononuclear phagocytes. Immunofluorescence and indirect peroxidase-antiperoxidase staining of articular cartilage (ACA) from 52% of 21 patients with RA and one with juvenile RA (JRA) showed presence of elastase in the superficial layer of microscopically intact but proteoglycan depleted pannus-free ACA. In histologically altered pannus-free RA-ACA superficial elastase deposits were found in 24% of the cases. Adjacent ACA sections contained IgG, C3, alpha 1-PI and rarely alpha 2-MG. RA-ACA below or surrounded by pannus showed close contact with intact and decaying PMN in 62% and 48% of the cases, respectively. ACA specimens from patients with degenerative disease and systemic lupus were negative. These findings strongly suggest that PMN leucocyte elastase is operative in the degradation of RA-ACA and JRA-ACA, and that this activity is largely dependent upon the presence of entrapped immune complexes in such cartilage.
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PMID:Degradation in vivo of articular cartilage in rheumatoid arthritis by leucocyte elastase from polymorphonuclear leucocytes. 705 Dec 54

Sera from 76 patients with diverse vasculitis, systemic lupus erythematosus (SLE) and hydralazine-induced lupus (HiL) were analysed by ELISA for their reactivity with native, reduced or urea-denatured MPO, respectively, as well as with bacterially expressed heavy and light subunits of MPO. All sera (n = 20) recognizing native MPO showed a positive reaction with reduced MPO, while 12 recognized the denatured protein. Most of the linear epitopes are located in the light subunit, since 9 MPO-positive sera recognized significantly the bacterially expressed, denatured light subunit, while only one serum recognized the bacterially expressed heavy subunit purified under denaturing conditions.
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PMID:Antineutrophil cytoplasmic autoantibodies (ANCA) recognizing a recombinant myeloperoxidase subunit. 750 31

In the present study, an analysis was made of the expression pattern of thrombospondin-1 (TSP1) and its receptor (CD36) in skin biopsies obtained from healthy volunteers and from patients with lichen planus, lupus erythematosus, cutaneous T-cell lymphoma and psoriasis vulgaris. Using monoclonal antibodies against TSP1 in biopsies from the healthy volunteers and from both clinically involved and uninvolved skin of the patients, a specific peroxidase-positive reaction was detected around the sweat glands in the dermis. In all cases investigated, the CD36-positive lesional keratinocytes remained TSP1-negative. These findings favour the hypothesis that CD36-positive keratinocytes might have some functional relevance via oxidized low-density lipoprotein and/or collagen fibrils, without any connection with TSP1.
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PMID:Expression of thrombospondin-1 (TSP1) and its receptor (CD36) in healthy and diseased human skin. 752 82

In systemic lupus erythematosus accompanied by the abnormal appearance of circulating immune complexes (ICs), Fc gamma receptor (FcR)-mediated IC handling in macrophages including Kupffer cells has been shown previously. However, sinusoidal endothelial cells (SECs) largely ingest soluble immunoglobulin (Ig) G-ICs through FcRs. In this study, the character, antigenic expression, and activity (i.e., ligand-binding capacity of SEC FcRs in NZB/NZW F1 lupus and NZW nonautoimmune mice) were immunohistochemically analyzed using monoclonal antibody (MAb) 2.4G2 to FcRs and peroxidase-antiperoxidase IgG as a ligand on cryosections. MAb 2.4G2 stained SECs and blocked the ligand binding of SEC FcRs in both mice strains. The staining intensities with MAb 2.4G2 in SECs and the FcR activities in SECs alone and all sinusoidal cells in both mice strains reached their maximum values at the age of 5 months. Staining intensities in NZB/W F1 were significantly higher at 1 and 2 months and lower at 9 months than those in NZW. The number of Kupffer cells detected by MAb F4/80 to macrophages in both mice strains gradually increased until 5 months, but their number in NZB/W F1 at 9 months was twice as large as that in NZW. In conclusion, SEC FcRs in mice are low-affinity FcRs that react with MAb 2.4G2. The data of FcR activity suggest no impairment of the FcR-mediated IgG-IC binding on SECs in NZB/W F1 in early life.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fc receptors in liver sinusoidal endothelial cells in NZB/W F1 lupus mice: a histological analysis using soluble immunoglobulin G-immune complexes and a monoclonal antibody (2.4G2). 754 88

It is known that activation of neutrophils or monocytes leads to the formation of hydrogen peroxide and the release of myeloperoxidase (MPO). We found that sulfamethoxazole was chlorinated by the combination of MPO, hydrogen peroxide, and chloride. The product, N-chlorosulfamethoxazole, is reasonably stable but reacts rapidly with a variety of compounds. The same product was formed by the reaction between sulfamethoxazole and hypochlorous acid, and dapsone was also N-chlorinated by the MPO system or hypochlorous acid. Although N-chlorination was not observed when sulfamethoxazole or dapsone was incubated with activated neutrophils, this is presumably because the chloramine products react rapidly with the cells. When radiolabeled sulfamethoxazole was incubated with activated neutrophils, covalent binding was observed. When radiolabeled sulfamethoxazole was incubated with MPO and hydrogen peroxide in the presence of albumin, covalent binding to the albumin occurred. Although binding to albumin occurred in the absence of chloride, it was increased by the presence of chloride. This suggests that N-chlorosulfamethoxazole may be one of several reactive metabolites of sulfamethoxazole that covalently bind to neutrophils. We suspect that covalent binding of arylamine drugs, such as sulfamethoxazole, to activated leukocytes is responsible for some of the adverse reactions associated with these drugs, especially adverse reactions that involve leukocytes such as agranulocytosis or drug-induced lupus.
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PMID:N-chlorination of sulfamethoxazole and dapsone by the myeloperoxidase system. 790 44

We describe 2 cases of a lupus syndrome induced by sulfasalazine in rheumatoid arthritis. All symptoms resolved and antihistone antibodies disappeared when sulfasalazine was discontinued. In one patient, perinuclear antineutrophil cytoplasmic antibodies with specificity for myeloperoxidase were found critically increased just before the occurrence of vasculitis.
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PMID:Sulfasalazine induced lupus in rheumatoid arthritis. 791 4

Drug-induced lupus is a serious side effect of certain medications, but the chemical features that confer this property and the underlying pathogenesis are puzzling. Prototypes of all six therapeutic classes of lupus-inducing drugs were highly cytotoxic only in the presence of activated neutrophils. Removal of extracellular hydrogen peroxide before, but not after, exposure of the drug to activated neutrophils prevented cytotoxicity. Neutrophil-dependent cytotoxicity required the enzymatic action of myeloperoxidase, resulting in the chemical transformation of the drug to a reactive product. The capacity of drugs to serve as myeloperoxidase substrates in vitro was associated with the ability to induce lupus in vivo.
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PMID:Transformation of lupus-inducing drugs to cytotoxic products by activated neutrophils. 772 10

Circulating antibodies to myeloperoxidase (MPO) have been described in a variety of vasculitic syndromes, drug-induced SLE and drug-induced nephritis. We have examined the autoantibody profile in acute sera from patients with antineutrophil cytoplasmic antibody-positive vasculitis (n = 8), drug-induced nephritis (n = 4), drug-induced lupus (n = 7), SLE (n = 27) and nephritis-associated with SLE (n = 17). Significant binding to purified MPO in ELISA was given by all sera from patients with vasculitis and drug-induced nephritis but ANA sought by indirect immunofluorescence on HEp-2 cells were not detected. Both anti-MPO and ANA were found in sera from patients with drug-induced lupus. Sera from patients with SLE or SLE nephritis did not contain high titres of anti-MPO antibodies but invariably contained ANA. Anti-MPO antibodies of both IgG and IgM classes were present in all sera from patients with drug-induced disease. Although the number of samples tested was small, sera from patients with drug-induced nephritis showed significantly greater median % binding of IgM to MPO compared with drug-induced SLE. Binding to MPO by IgG in these sera was not significantly different. These findings suggest that the mechanism of interaction between hydralazine and the immune system in the two drug-induced autoimmune diseases studied may contribute to their distinct clinical features.
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PMID:Autoantibodies to myeloperoxidase in idiopathic and drug-induced systemic lupus erythematosus and vasculitis. 816 72

Peripheral blood leukocytes contain a variety of enzymes that are capable of metabolising xenobiotics. The enzyme myeloperoxidase (MPO) appears to be the most important for drug metabolism. MPO is a peroxidase/oxidase and generates the powerful oxidant hypochlorous acid. MPO- or MPO-generated oxidants are capable of oxidizing a wide variety of compounds and a broad range of functional groups, especially those that contain nitrogen and sulfur. Leukocytes have a role in immune response; therefore, reactive intermediates generated by leukocyte metabolism of xenobiotics may have a role in idiosyncratic drug reactions, particularly those that are immune-mediated such as drug-induced lupus or agranulocytosis.
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PMID:Myeloperoxidase-mediated activation of xenobiotics by human leukocytes. 823 77

Autoantibodies directed against myeloperoxidase and elastase have been found in patients developing hydralazine-induced lupus and hydralazine-induced isolated glomerulonephritis. The aim of this study was to investigate influence of hydralazine and dihydralazine upon myeloperoxidase and elastase enzyme activity. Using a 4-aminoantipyrin in vitro system, dihydralazine was 2.5 times as potent in inhibiting myeloperoxidase activity as compared to hydralazine. The corresponding Ki-values were 4 microns M for dihydralazine and 25 microM for hydralazine. When using 2.2'-azino-bis-3-ethyl-benzothiazoline-6-sulphonic acid system inhibition was found at lower concentrations. Furthermore, the difference between the compounds was not so pronounced as seen for 4-aminoantipyrin. The Ki-values for hydralazine and dihydralazine were 1.2 and 1.4 microM respectively. Complete inhibition was seen for both compounds at concentrations above 7.5 microM. Hydralazine binds to elastase, but neither hydralazine nor dihydralazine inhibited elastase enzyme activity.
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PMID:Interaction of myeloperoxidase and elastase enzyme activity with the antihypertensive agents hydralazine and dihydralazine. 824 10


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