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)

Surface expression of 16 different membrane molecules was analyzed in peripheral blood and synovial fluid monocytes from patients with rheumatoid arthritis and reactive arthritis compared to controls. The most significant findings were modulated expression of function-associated FcRI, CR1, CR3, MHC class II and activation-associated CD31, M5, and M6 molecules in arthritis patients compared to controls. Of these molecules, only upregulated expression of MHC class II has previously been reported in synovial fluid monocytes of patients with rheumatoid arthritis.
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PMID:Phenotypic analysis of functionally associated molecules on peripheral blood and synovial fluid monocytes from arthritis patients. 143 82

Activation of human neutrophils (PMN) is accompanied by rapid upregulation of CR1, the C3b receptor, and CR3, the iC3b receptor, which also serves as the PMN's major adherence protein. This is necessary for migration and phagocytosis, but the extent of expression of these proteins on PMN at inflammatory sites has not been determined. We used monoclonal antibodies and flow cytometry to assess CR1 and CR3 expression on PMN in bronchoalveolar lavage (BAL) fluid of cystic fibrosis (CF) patients chronically infected with pseudomonas and in sterile joint fluid of arthritis patients. Resting peripheral blood PMN from these patients and normals expressed similar low levels of CR1 and CR3, and the patients' PMN increased CR1 and CR3 expression normally when stimulated in vitro. CR3 expression on CF BAL PMN was 90 +/- 12% of that on the same patient's blood cells stimulated in vitro with FMLP. In contrast, CR1 expression on BAL PMN was only 27 +/- 8% of that on stimulated blood cells. Similar results were obtained for joint PMN. This pattern could be reproduced in vitro by treating FMLP-stimulated blood cells with BAL supernatants or with pseudomonas or PMN elastase. The serine protease inhibitors, PMSF and alpha 1-antitrypsin prevented the lavage supernatant from reducing CR1 expression, while metalloprotease inhibitors had no effect. Treatment of PMN with elastase in vitro decrease their ability to kill opsonized Pseudomonas aeruginosa. These results suggest that PMN at inflammatory sites have maximally upregulated expression of their complement receptors, but that CR1 is then cleaved by proteolysis in situ. Although not related to the basic defect in CF, this may interfere with efficient phagocytosis and contribute to the CF patient's inability to eradicate chronic lung infection.
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PMID:Complement receptor expression on neutrophils at an inflammatory site, the Pseudomonas-infected lung in cystic fibrosis. 250 78

The expression of leukocyte adhesion molecules CR3 (CD11b) and p150,95 (CD11c) in synovial tissue was evaluated immunohistochemically. Although a significant proportion of synoviocytes in normal and osteoarthritic synovial membranes expressed the leukocyte common antigen and CR3, very few expressed the p150,95 molecule. In contrast, p150,95 was more evident in rheumatoid synovial membranes. Expression of this molecule was strongest in synovial membranes with a prominent macrophage infiltrate and accumulation of mononuclear phagocytes at the joint surface; p150,95 was also present on interdigitating cells in lymphoid collections. The patterns of expression suggest that these leukocyte adhesion molecules may be important in the diapedesis of mononuclear phagocytes into and through inflamed synovial membranes, as well as in cellular interactions within rheumatoid synovial membranes.
Arthritis Rheum 1989 Aug
PMID:Increased expression of p150,95 and CR3 leukocyte adhesion molecules by mononuclear phagocytes in rheumatoid synovial membranes. Comparison with osteoarthritic and normal synovial membranes. 256 74

Lymphocytes displaying iC3b (Type 3) complement receptors (CR3) were quantified by flow cytometry in patients with systemic lupus erythematosus. The percentages and absolute numbers were compared to age and sex matched controls. Total CR3+ lymphocytes identified by the monoclonal antibodies OKM1 or Leu 15 were significantly decreased in patients with symptomatic arthritis, serositis or vasculitis and those with lupus nephritis, whereas values for CR3+ lymphocytes in patients with inactive disease were similar to normal donors. The phenotype of CR3+ lymphocytes was markedly different in patients with active SLE. In normals granular lymphocytes bearing Fc receptors for IgG (L cells) comprised two-thirds of CR3+ lymphocytes. However, in SLE this subset was reduced to 20% and there was a corresponding increase in CR3+ lymphocytes co-expressing the T3 marker. Percentages of CR3 T4+ but not CR3+ T8+ lymphocytes were significantly increased in SLE. Although patients with active disease were lymphopenic, absolute numbers of CR3+ lymphocytes co-expressing T cell markers were similar to normal controls. Since L cells are non-specific suppressors of Ig production, the reduction of this subset along with the increase in CR3 T4+ cells could contribute to unregulated antibody production characteristic of SLE.
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PMID:Studies on human blood lymphocytes with iC3b (type 3) complement receptors: III. Abnormalities in patients with active systemic lupus erythematosus. 295 74

We investigated the involvement of polymorphonuclear granulocytes (PMN) and monocytes in cartilage degradation in immune complex-mediated arthritis (ICA). ICA induced with lysozyme-antilysozyme in the murine knee joint is characterized by a major influx of PMNs followed by monocytes and marked cartilage proteoglycan (PG) depletion develops within 2 days. Around 60% of 35S-prelabeled PG is lost at day 2. Influx of cells was manipulated using interleukin-1 (IL-1) receptor antagonist (IL-1ra) or antibodies to adhesion molecules. Cellular infiltrate was analyzed on hematoxylin-stained joint sections. Early systemic treatment with IL-1ra highly reduced PMN influx, whereas monocyte influx was hardly diminished. PG loss was not significantly reduced, declining from 62% in controls to 47% in IL-1ra-treated mice. Total blockade of cell influx was found after intravenous treatment with monoclonal antibodies 5C6 (anti-CD11b/CD18:anti-CR3) or NIMP.R14 (25-30 kDa protein mainly present on PMN) and PG loss was reduced to 5-10%. A similar reduction was observed after prior depletion of circulating PMNs with total body irradiation. Because amounts of IL-1 produced in leukopenic and control arthritic joints are comparable, this suggests that IL-1 is only marginally involved in PG loss in the first phase of ICA. This study indicates that monocytes rather than PMN might be involved in PG loss in this form of arthritis, either directly or by local activation of synovial layer cells of the joint.
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PMID:Monocytes/macrophages rather than PMN are involved in early cartilage degradation in cationic immune complex arthritis in mice. 906 Apr 49

Anti-inflammatory drugs have been suggested as a possible treatment for Alzheimer's disease (AD). The association of immune proteins and immune-competent microglial cells with senile plaques (SP) in both AD and normal aging suggests that these drugs may be able to modify the course of AD, either by interfering with SP formation or by suppressing the inflammation associated with SP. We compared postmortem brain tissue from elderly, nondemented, arthritic patients with a history of chronic nonsteroidal anti-inflammatory drug (NSAID) use (n = 32, aged 77 +/- 7 years) and nondemented control subjects with no history of arthritis or other condition that might promote the regular use of NSAIDs (n = 34, aged 77 +/- 6 years). In both the NSAID-treated group and control subjects, 59% of patients had some SP. There was no difference between the two groups in the mean number of plaques or in the number of specific SP subtypes (diffuse or neuritic). The degree of neurofibrillary pathology was also similar. Activated microglia were identified using CR3/43, an anti-MHC class II antibody. Both patient age and the presence of SP correlated positively with the number of CR3/43+ microglia (p < 0.02), whereas NSAID use was associated with less microglial activation (p < 0.01). Control patients with SP had almost three times the number of activated microglia as NSAID-treated patients with SP (11 versus 4 cells/mm2, p < 0.02). These results suggest that if NSAID use is effective in treating AD, the mechanism is more likely to be through the suppression of microglial activity than by inhibiting the formation of SP or neurofibrillary tangles.
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PMID:Nonsteroidal anti-inflammatory drug use and Alzheimer-type pathology in aging. 956 83

Activation of each complement initiation pathway (classical, alternative, and lectin) can lead to the generation of bioactive fragments with resulting inflammation in target organs. The objective of the current study was to determine the role of specific complement activation pathways in the pathogenesis of experimental anti-type II collagen mAb-passive transfer arthritis. C57BL/6 mice were used that were genetically deficient in either the alternative pathway protein factor B (Bf(-/-)) or in the classical pathway component C4 (C4(-/-)). Clinical disease activity was markedly decreased in Bf(-/-) compared with wild-type (WT) mice (0.5 +/- 0.22 (n = 6) in Bf(-/-) vs 8.83 +/- 0.41 (n = 6) in WT mice (p < 0.0001)). Disease activity scores were not different between C4(-/-) and WT mice. Analyses of joints showed that C3 deposition, inflammation, pannus, cartilage, and bone damage scores were all significantly less in Bf(-/-) as compared with WT mice. There were significant decreases in mRNA levels of C3, C4, CR2, CR3, C3aR, and C5aR in the knees of Bf(-/-) as compared with C4(-/-) and WT mice with arthritis; mRNA levels for complement regulatory proteins did not differ between the three strains. These results indicate that the alternative pathway is absolutely required for the induction of arthritis following injection of anti-collagen Abs. The mechanisms by which these target organ-specific mAbs bypass the requirements for engagement of the classical pathway remain to be defined but do not appear to involve a lack of alternative pathway regulatory proteins.
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PMID:Alternative complement pathway activation is essential for inflammation and joint destruction in the passive transfer model of collagen-induced arthritis. 1684 3

We have recently shown that resistin is a key mediator of arthritis accumulating in the inflamed joints and exerting its pro-inflammatory properties independently of TNFalpha. Here we evaluate neutrophils as a cellular source of resistin. Human neutrophils were subjected to subcellular fractionation where the presence of resistin was assessed using western blot, ELISA, and mass spectrometry. Presence of resistin on the neutrophil surface was visualized by flow cytometry. More than 95% of the neutrophils in circulation and in synovial fluid express resistin on their surface. Stimulation of mature neutrophils with fMLF induced release of resistin into supernatants and increased expression of resistin on the surface. Resistin is mobilized simultaneously with lactoferrin, a protein found in specific granules, and with granule-stored CR3/CD11b. Subcellular fractionation of human neutrophils demonstrated the presence of resistin in azurophilic and in specific granules. Here we show that neutrophils have two pools of resistin, the major one exists in specific granules, and the second on their cell membrane. Release of resistin from the neutrophil granules probably serves the main source of resistin at the site of inflammation.
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PMID:Resistin is stored in neutrophil granules being released upon challenge with inflammatory stimuli. 1977 5