Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wistar rats (type II collagen-induced arthritis-susceptible) and PVG.RT1u rats (arthritis-resistant) were immunised with type II collagen and histological changes in the synovial tissues of the hind feet and in the popliteal lymph nodes draining these feet were examined and compared with unimmunised rats. There were no apparent differences in the joints of unimmunised rats of each strain, but the popliteal lymph nodes of the Wistar rats appeared more "activated", suggesting possible differences between strains in the continuous, low-grade release of antigens from the joints. Whilst the joints of arthritic rats showed the most marked histological changes, the joints of immunised PVG.RT1u rats and of non-arthritic Wistar rats showed some minor changes in the synovia and loss of cartilage with a concomitant increase in the size of the popliteal lymph nodes. The number of mast cells per unit area increased in the lymph nodes of immunised PVG.RT1u rats in proportion to the size increase, but decreased in those draining arthritic Wistar rat feet. The number of mast cells per unit area of synovium decreased most in arthritic feet and the staining pattern of the mast cells altered in the most severely arthritic feet, suggesting a change in mast cell population. These differences in mast cells may be directly related to whether or not clinical arthritis develops in a particular joint. Further study of mast cell sub-populations is warranted.
 ...
PMID:Type II collagen induced arthritis: comparison of histological changes in arthritis-susceptible and arthritis-resistant rats. 150 2

The relationship between production of IgE and collagen-induced arthritis in mice was examined. Collagen-specific IgE was produced as a consequence of immunization of DBA/1 mice with chicken type II collagen emulsified in CFA. We observed a rise in collagen-specific IgE antibody levels at the onset of CIA clinical and histologic signs in DBA/1 mice. This rise in IgE paralleled that of IgG2a anticollagen antibodies, an isotype implicated in the pathogenesis of CIA by other laboratories. The collagen-specific IgE contained in the plasma of mice with CIA could arm basophils for Ag- (collagen) dependent degranulation. Collagen-specific IgE may thus contribute to CIA by promoting mast cell degranulation in the synovia of susceptible mice immunized with chick type II collagen; but, further work is required to establish such a role for IgE in CIA. However, genetic differences in disease susceptibility could not be accounted for by quantitative differences in collagen-specific IgE production. Further, comparable levels of IgE anticollagen antibodies were observed in animals with active CIA and after spontaneous remission, thereby confirming that the presence of such antibodies is insufficient for disease. Total IgE levels peaked just before spontaneous remission indicating active production of IL-4. IL-4 was administered to animals with CIA to determine if this lymphokine could be involved in the remission process. IL-4 facilitated remission of CIA. Enhanced total IgE production may thus be a marker for activation of Th2 cells that produce lymphokines such as IL-4 and IL-10, factors that may be involved in the spontaneous remission process.
 ...
PMID:Collagen-induced arthritis in mice. Relationship of collagen-specific and total IgE synthesis to disease. 175 95

The presence of circulating IgG, IgA and IgM antibodies to native cartilage collagens in some patients with rheumatoid arthritis (RA) suggests that an autoimmune response to cartilage collagens may be involved in the pathogenesis of RA. However, the relevance of such antibodies to the pathological process remains unclear, and it is likely that many humoral and cellular derived factors combined to trigger events leading to the chronicity of the rheumatoid lesion. Since histological and biochemical studies have suggested the involvement of mast cells in the rheumatoid joint, we have studied the frequency of IgE antibodies directed against the cartilage collagens type II, IX and XI in patients with active rheumatoid disease. Of the 91 patients' sera tested, 32 had significant levels of IgE anti-cartilage collagen antibodies when compared with non-arthritic controls. Total serum IgE levels did not correlate with the presence of IgE anti-collagen antibodies, nor were any patients positive for IgE antibodies to fibronectin, a widely distributed extracellular matrix component. These results are consistent with an allergic type I hypersensitivity reaction to cartilage antigens in RA involving mast cell and basophil degranulation.
 ...
PMID:Serum IgE anti-cartilage collagen antibodies in rheumatoid patients. 186 71

Arthritis resembling human rheumatoid arthritis is produced in rats either by immunization with type II collagen or injection of complete Freund's adjuvant. The development of arthritis in both models may be mediated by a T cell-derived, type II collagen-specific protein that has been termed arthritogenic factor. Here, the morphologic changes produced after intraarticular injection of this factor were determined. T cell lines were derived from type II collagen-immunized rats. Arthritogenic factor was isolated from culture supernatants by affinity chromatography on type II collagen-conjugated Sepharose and injected into rat knees. The synovium covering the infrapatellar fat pad was examined by light and electron microscopy at 6 hours to 7 days after injection. By 6 hours, the synovium and fat pad were edematous and heavily infiltrated with neutrophils and a few mononuclear cells. Fibrin was present in the synovium and joint space. Most mast cells had partially degranulated. By 24 hours, the infiltrate became primarily mononuclear and fewer neutrophils were seen. Fat necrosis and edema occurred in the subsynovium. By 48 hours and 7 days, the synovium was hyperplastic, some fibrin persisted, and macrophages were present. Control knees, injected with material obtained from T cell lines established with the antigen, ovalbumin, and subjected to type II collagen affinity chromatography, had less fibrin deposition, milder cellular infiltrates, and less mast cell degranulation than knees injected with arthritogenic factor. These studies suggest that arthritogenic factor stimulates acute cellular infiltration and mast cell secretion which is followed by fat necrosis, synovial hyperplasia, and mononuclear cell infiltration.
 ...
PMID:Intraarticular injection of arthritogenic factor causes mast cell degranulation, inflammation, fat necrosis, and synovial hyperplasia. 339 61

The therapeutic potential of salbutamol, a beta2-adrenergic agonist, was explored in collagen-induced arthritis. This study was based on a report that salbutamol, by elevating intracellular cAMP, inhibits IL-12 production by macrophages and dendritic cells, thus preventing Th1 development. Ten-week-old male DBA/1 mice were immunized by intradermal injection of type II collagen in CFA. Arthritis developed 15-30 days later and the mice were treated after onset of disease with salbutamol, 200 microgram i.p. After 10 days, the mice were sacrificed, and the hind paws were evaluated histologically. Salbutamol, 200 microgram daily or every other day, had a profound therapeutic effect on the clinical progression of arthritis, as assessed by clinical score and paw thickness. The therapeutic effect was dose dependent. Daily administration of 200 microgram of salbutamol offered the best protection against joint damage, as assessed by histology. In vitro, salbutamol reduced IL-12 and TNF-alpha release by peritoneal macrophages in a dose-dependent manner, as well as TNF release by synovial cells from arthritic mice. Ex vivo, draining lymph node cells of the salbutamol-treated arthritic mice showed a diminished CII-specific IFN-gamma production and proliferation. In vivo, salbutamol specifically blocked mast cell degranulation in joint tissues. In conclusion, salbutamol has important effects on the immunoinflammatory response and a significant therapeutic action in collagen-induced arthritis.
 ...
PMID:The beta2-adrenergic agonist salbutamol is a potent suppressor of established collagen-induced arthritis: mechanisms of action. 1022 75

Mice with a disrupted gp49B gene, which encodes gp49B1 that is expressed on certain hematopoietic cells and has two immunoreceptor tyrosine-based inhibitory motifs (ITIM), exhibit augmented FcepsilonRI-initiated mast cell degranulation and resultant tissue edema. gp49B1-deficient (gp49B(-/-)) mice also exhibit exaggerated lipopolysaccharide (LPS)-induced intravascular neutrophil aggregation leading to cutaneous microangiopathy. To determine whether gp49B(-/-) mice exhibit elevated cytokine and chemokine levels leading to pathologic inflammation, we quantified clinical and morphologic parameters of arthritis and tissue levels of contributory mediators in gp49B(-/-) and gp49B1-sufficient (gp49B(+/+)) mice injected with anti-type II collagen monoclonal antibody (mAb) and LPS. Clinical scores for joint swelling and histological assessments of synovial thickness and cartilage matrix depletion at day 7 were significantly 2.3- to 2.5-fold greater and were more prolonged in gp49B(-/-) mice. At day 5, the amounts of IL-1beta, macrophage inflammatory protein (MIP)-1alpha, and MIP-2 were 2.1-, 2.5-, and 12-fold greater in joint extracts from gp49B(-/-) mice. A significant 2.7-fold more neutrophils infiltrated the synovium of gp49B(-/-) mice at day 7, and neutrophilia persisted with the delayed resolution of the synovitis. mAb-mediated depletion of neutrophils prevented the synovitis in both strains. Thus, gp49B1 counter-regulates the cytokine and chemokine induction and attendant neutrophilia that are all essential for synovitis and cartilage matrix depletion.
 ...
PMID:gp49B1 deficiency is associated with increases in cytokine and chemokine production and severity of proliferative synovitis induced by anti-type II collagen mAb. 1582 66

Our previous study showed that the number of mast cells was increased in the inflamed paws of collagen-induced arthritis in mice, and treatment with a mast cell-stabilizing compound effectively suppressed the development of collagen-induced arthritis. A recent in vitro study showed that mast cells express cysteinyl leukotriene type 1 receptor, and that a cysteinyl leukotriene type 1 receptor antagonist inhibits the production of TNF-alpha by mast cells. To further investigate the role of mast cells in vivo, we evaluated the therapeutic effects of a cysteinyl leukotriene type 1 receptor antagonist, montelukast, on the development of collagen-induced arthritis in mice. Montelukast (10 mg/kg/day) or vehicle was orally administered to mice for 12 weeks, starting 6 weeks after immunization with bovine type II collagen. Treatment with montelukast significantly reduced clinical scores and X-ray scores of collagen-induced arthritis, and decreased the number of mast cells in the inflamed paws of collagen-induced arthritic mice. Immunohistochemical analysis revealed that mast cells in the inflamed synovium were one of the major cells producing TNF-alpha and that the number of TNF-alpha positive mast cells was significantly reduced by treatment with montelukast. Furthermore, TNF-alpha and SCF mRNA levels in the paws of collagen-induced arthritic mice were markedly decreased by montelukast treatment. Montelukast may lead to a beneficial therapeutic effect by inhibiting TNF-alpha production by mast cells.
 ...
PMID:Pathophysiological role of mast cells in collagen-induced arthritis: study with a cysteinyl leukotriene receptor antagonist, montelukast. 1694 72