Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human polymorphonuclear neutrophil (PMN) granule extract (25 mug of protein) released 60 percent of the available 35SO4 from labeled rabbit articular cartilage in 0.5 hour at neutral pH. N-acetyl-L-alanyl-L-alanyl-L-prolyl-L-alanine choloromethyl ketone (NAcAAPACK), a specific elastase inhibitor, was only minimally effective against whole granule extract, and N-alpha-tosyl-L-lysine chloromethyl ketone, which inhibits trypsin but not elastase, was completely ineffective. Preparative disc-gel electrophoresis of PMN granule extract revealed two separate regions with independent activity against 35SO4-labeled cartilage. One region contained elastases and when tested alone, was completely inhibited by NAcAAPACK. The other contained lysozyme and two esterases active against N-acetyl-L-phenylalanine-alpha-naphthol. Purified lysozyme proved inactive, suggesting that the chymotrypsin-like esterases were responsible for proteoglycan degradation by this region of the gel.
Arthritis Rheum
PMID:Identification of neutral proteases in human neutrophil granules that degrade articular cartilage proteoglycan. 23 25

As the lysozyme story continues to unfold, rheumatic disease is one area where the study of this fascinating protein will be most important. The special biochemical features of lysozyme--its hexosaminidase function, its ability to bring about transglycosylation, its homology to alpha-lactalbumin, and its cationic nature--suggest that the connective tissues may prove to be the key to the understanding of the function of lysozyme. As methods for its accurate measurement become standardized, better data on the activity of the enzyme in various tissues and body fluids, in both health and disease, will be forthcoming. As additional studies are done to ascertain which of the hypothetical functions attributed to lysozyme are of significance in vivo, it will be the student of the connective tissues and the diseases thereof who can be expected to profit most from an udnerstanding of the role of lysozyme in mammalian biology.
Semin Arthritis Rheum 1976 Aug
PMID:Connective tissue lysozyme in health and disease. 78 4

Lysozyme and lactoferrin levels were measured in 71 synovial fluids (SF) of patients with traumatic effusions, osteoarthritis, rheumatoid arthritis, pseudogout, septic arthritis, and gout, as well as in 91 synovial fluids graded according to their neutrophil count. Elevated lysozyme levels were found in all the inflammatory arthritides and also in osteoarthritis. Lactoferrin levels were not increased in osteoarthritis but displayed a close correlation to the extent of the inflammatory response as judged by SF neutrophilia. The ratio of lysozyme to lactoferrin decreased progressively with increasing SF neutrophilia. In vitro experiments showed that lactoferrin is released from neutrophils isochronously with lysozyme and beta-glucuronidase. Lactoferrin was not found in hyaline cartilage, a tissue known to contain lysozyme. These results are consistent with belief that SF lysozyme has a major derivation from both cartilage and neutrophils, and that lactoferrin arises only from neutrophils. These findings indicate that the simultaneous measurement of lysozyme and lactoferrin provides a potentially useful index of both joint inflammation and cartilage degradation.
Arthritis Rheum
PMID:Lactoferrin and lysozyme levels in synovial fluid: differential indices of articular inflammation and degradation. 83 40

Lactoferrin (LF) has been assayed by radioimmunoassay in plasma and arthritic exudates and compared with lysozyme (LZ) levels and leukocyte counts. The mean LF concentration in 38 rheumatoid arthritis (RA) exudates was 9.1 mg/l (range 0.02-39.2). In 30 non-RA exudates LF was 3.3 mg/l (range 0.01-14.6). The corresponding LZ levels were 7.4 mg/l (range 2.5-18.5) in RA and 4.7 (range 1.0-12.5) in non-RA fluids. Exudate/plasma ratios were much higher for LF than for LZ and higher in RA than in non-RA exudates, whereas leukocyte counts did not differ. The LF/leukocyte count ratio was significantly higher in RA than in the non-RA group. The data suggest a more prominent release of neutrophilic granulocyte components in RA than in non-RA arthritis.
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PMID:Lactoferrin and lysozyme in arthritic exudates. 92 Feb 51

Monosodium urate (MSU) crystals induced prompt release of lysozyme, and slower release of beta-glucuronidase, alpha-mannosidase, and lactic dehydrogenase (LDH) from polymorphonuclear leukocytes. At increasing crystal concentrations, an increasing delay in the apparent onset of beta-glucuronidase release was detected which appears to be due to selective absorption of enzyme activities to the MSU crystals: beta-glucuronidase greater than LDH greater than alpha-mannosidase greater than lysozyme. Lysosomal enzyme adsorption by MSU crystals may then contribute to experimental error or may modulate gouty inflammation.
Arthritis Rheum
PMID:Adsorption of polymorphonuclear leukocyte lysosomal enzymes to monosodium urate crystals. 92 26

Arthritic and histologically normal joints from swine in which arthritis had been produced by the intravenous inoculation of Erysipelothrix rhusiopathiae were used as a source of fluids for lysosomal enzyme determinations. Mean lysozyme activities in synovias from arthritic and histologically normal joints were 16.60 and 5.79 mug/ml, respectively. Acid phosphatase (ACP) was increased more than 8 times the activity in histologically normal joints, but there was no relationship between lysozyme and ACP, indicating the probability that 1 of these enzymes came from another source. The cytoplasmic enzyme, lactic dehydrogenase (LDH), was increased in proportion to ACP, indicating that cell death and not selective extrusion of lysosomal enzymes during phagocytosis was an important mechanism of enzyme release in arthritic joints. Lysozyme activities in synovias from histologically normal joints were often increased above companion serum concentrations, indicating the enzyme has a special role in the joint. Also, the ratio of activities of lysozyme to ACP in pig buffy coat lysates was different from the ratio of the 2 enzymes in synovias from arthritic joints.
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PMID:Erysipelas arthritis in swine: lysosomal enzyme levels in synovial fluids. 94 4

Cell walls of Mycobacterium smegmatis were able to produce much more severe arthritis in rats than the delipidated cells, whereas cell envelope and cell membrane fractions were unable to produce the disease. The lysozyme-solubilized product was able to produce mild disease with only 30% of incidence with an optimum dose, whereas the higher and the lower doses did not produce the disease. The rats immunized with cell envelope, cell membrane fraction and nonarthritogenic doses of lysozyme-solubilized product were protected against the subsequent homologous and heterologous challenge of delipidated cells. It was discussed that this preventative effect can be the result of antigenic competition between the arthritogenic and nonarthritogenic components of M. smegmatis. On the other hand, all the fractions separated here were able to serve as an immunoadjuvant in terms of inducing delayed hypersensitivity to ovalbumin in guinea pigs.
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PMID:Preparation of various fractions from Mycobacterium smegmatis, their arthritogenicity and their preventive effect on adjuvant disease. 108 56

Acute cartilage degradation was produced in rabbits by the intravenous injection of crude papain. This resulted in a significant rise in serum lysozyme in 97% of the animals, as well as a fall in the residual lysozyme content of auricular and costal cartilage. The rise in serum lysozyme paralleled the rise in serum chondroitin sulfate. The source of the rise in lysozyme appeared to be the release of extracellular, nonlysosomal lysozyme from the cartilage matrix. Serum lysozyme elevation in arthritic disorders may reflect cartilage degradation.
Arthritis Rheum
PMID:Effects of acute cartilaginous injury on serum and cartilage lysozyme levels. 113 Dec 82

A novel cationic immune-complex-mediated arthritis (ICA) model was developed in mice. The highly cationic protein lysozyme was coupled to poly-L-lysine (PLL) and injected intra-articularly into the knee joint of the mouse, shortly after systemic administration of specific antibodies. A vehement joint inflammation developed, characterized by severe joint swelling and the influx of predominantly polymorphonuclear (PMN) leukocyte. Unique properties were combined in this protein. First, an excellent retention of the antigen in joint structures was found, facilitating sufficient IC formation in the synovial tissue and at the cartilage surface. Secondly, PLL.lysozyme appeared to be a potent inducer of interleukin-1 (IL-1). Similar IL-1 production was measured at 6 hours, in both immune or nonimmune mice. Neutralization with antibodies against either IL-1 alpha or IL-1 beta revealed that IL-1 alpha was the dominant cytokine. Resident cells were responsible for this IL-1 production since a comparable IL-1 signal was measured after intra-articular injection of PLL.lys in neutropenic mice. We further investigated whether IL-1 and complement factors were involved in the onset of this ICA. Neutralizing the IL-1 production with antibodies directed against IL-1 alpha and beta showed a significant decrease in joint swelling. Complement depletion by cobra venom factor also prevented the onset of arthritis for the greater part. Only a minor swelling remained at 6 hours after eliciting arthritis, which was similar to the swelling after injecting the antigen alone and probably reflects IL-1 mediated inflammation. In this study, the authors show a synergistic action of IL-1 and complement in the onset of cationic ICA. Unique properties of the antigen such as excellent retention and its ability to induce IL-1 are combined within one molecule and make this antigen arthritogenic in the presence of antibodies and complement activation.
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PMID:Cationic immune complex arthritis in mice--a new model. Synergistic effect of complement and interleukin-1. 160 10

The aims of the present study were to define, under in vivo conditions, factors governing antigen binding and persistence in the rat joint and to establish a chronic arthritis model by means of a natural polycation. The influence of size as well as charge on antigen handling was examined using a range of chemically cationized proteins and natural polycations. Arthritis was induced by intraarticular challenge in preimmunized rats. Immunofluorescence studies revealed that not only pI, which must exceed pH 8-9, but also molecular size was a decisive parameter: only antigens of more than 40 kD were able to persist for significant periods in joint structures. All existing models of antigen induced chronic arthritis in rodents utilize chemically cationized proteins. We extended this system to natural polycations by showing that lysozyme (pI 11.3; MW 14 kD) in tetrameric, charge conserved form (MW 56 kD) as a model-antigen was able to induce chronic arthritis in the rat. After intraarticular challenge of preimmunized animals the course of inflammation was assessed both by 99mTechnetium-pertechnetate (99mTc) scintigram and from the histology. In contrast to monomeric lysozyme, which evoked only a transient inflammatory response (less than two weeks), tetrameric lysozyme induced a chronic arthritis, which still persisted at day 90. Our results show that the ability of cationic antigens to trigger chronic arthritis is vitally size dependent. This is also the first report of a natural polycation acting as an arthritogen, thus providing an experimental basis justifying the search for cationic microbial antigens in human post infectious reactive arthritis.
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PMID:Handling of cationic antigens in the joint and induction of chronic allergic arthritis. In vivo studies in the rat. 168 52


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