ovalbumin and Synovitis

The objective of this study was to explore the feasibility and value of high-resolution ultrasound and contrast-enhanced ultrasound in evaluation of synovitis in rabbit knee joint in antigen-induced arthritis (AIA). Thirty-six rabbits were divided into three groups, each injected with different doses of ovalbumin (OVA) into the right knee joint. On week 1 and 4, 6 randomly selected in each group were killed. Each knee joint undergone the high-resolution ultrasound to measure capsule thickness and contrast-enhanced ultrasound to measure synovium thickness. The results from the ultrasound examinations were compared with those of pathologic examinations. Different OVA doses resulted in different modeling success rate, different pathological synovitis score, and different capsule and synovium thickness measured by ultrasound. The diagnostic accuracy of synovitis by ultrasound was high. The ultrasound measurement revealed that the capsule thickness on week 4 was lessened than that on week 1, while the synovial thickness on week 4 was greater than that on week 1. Both the joint capsule and synovium thickness measured by ultrasound were significantly and positively correlated to the pathologic synovitis score (P < 0.05). The synovial thickness on week 4 is more correlated to the synovitis score than the capsule thickness, rather than that on week 1. Injection of OVA of different doses results in different modeling success rate and synovitis severity. The high-resolution ultrasound and contrast-enhanced ultrasound can be used to determine whether the AIA was made successfully and evaluate the synovitis severity. In chronic inflammatory phase, the contrast-enhanced ultrasound has better effect.

Topics: Animals; Arthritis, Experimental; Contrast Media; Feasibility Studies; Female; Knee Joint; Male; Ovalbumin; Predictive Value of Tests; Rabbits; ROC Curve; Severity of Illness Index; Synovial Membrane; Synovitis; Time Factors; Ultrasonography

Activation of the alpha7 receptor (α7nAChR) has been shown to be important in inflammation and immune regulation, and is also essential in the neural cholinergic anti-inflammatory pathway. The aim of this study was to investigate the role of α7nAChR in the development of experimental arthritis and immune activation. Mice lacking the α7nAChR were immunized with collagen II and the development of arthritis was assessed. Another group of α7nAChR-deficient mice was immunized with ovalbumin, spleen and lymph node cells were isolated and the proliferative responses to restimulation with ovalbumin or concanavalin A were investigated. We could demonstrate significantly milder arthritis and less cartilage destruction, together with a decrease of T cell content in lymph nodes in mice lacking the α7nAChR compared to wild-type controls. In addition, mice lacking the α7nAChR had a deficient proliferative response to concanavalin A, whereas antigen presentation-dependent proliferation was not affected. These results indicate important roles for α7nAChR in arthritis development as well as in regulation of T cell-dependent immunological mechanisms. In addition, the data implicate α7nAChR as a therapeutic target for modulation of adaptive immune responses.

Topics: Adaptive Immunity; alpha7 Nicotinic Acetylcholine Receptor; Animals; Arthritis, Experimental; Cartilage, Articular; Cell Proliferation; Concanavalin A; Female; Flow Cytometry; Lymph Nodes; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mitogens; Ovalbumin; Receptors, Nicotinic; Severity of Illness Index; Spleen; Synovitis; T-Lymphocytes

High mobility group box chromosomal protein 1 (HMGB1) is a nuclear protein that acts as a pro-inflammatory mediator following extracellular release. The protein is aberrantly expressed extracellularly in the settings of clinical and experimental synovitis. Therapy based on HMGB1 antagonists has shown encouraging results in experimental arthritis and warrants further scientific exploration using independent methods. In the present study we asked whether nuclear sequestration of HMGB1 preventing HMGB1 release would be beneficial for synovitis treatment.. Oxaliplatin-based therapy was evaluated in collagen type II-induced arthritis in DBA/1 mice by clinical scoring and immunostaining of articular tissue. Oxaliplatin is an antineoplastic platinum-based compound that generates DNA adducts which tightly bind HMGB1. Secretion and intracellular location of HMGB1 were assessed by a novel HMGB1-specific ELISPOT assay and immunofluorescent staining.. Intraperitoneal injections of oxaliplatin in early collagen type II-induced arthritis trapped HMGB1 with a distinct biphasic response pattern. Oxaliplatin therapy showed beneficial results for approximately 1 week. Microscopic evaluation of synovitis during this period showed strong nuclear HMGB1 staining in the oxaliplatin treated animals with much lower quantities of extracellular HMGB1 when compared to control treated animals. Furthermore, cellular infiltration, as well as cartilage and bone damage, were all reduced in the oxaliplatin treated group. A dramatic and as yet unexplained clinical relapse occurred later in the oxaliplatin exposed animals, which coincided with a massive synovial tissue expression of extracellular HMGB1 in all treated animals. This rebound-like reaction was also accompanied by a significantly increased incidence of arthritis in the oxaliplatin treated group. These results indicate a distinct temporal and spatial relationship between the clinical course of disease and the cellular localization of HMGB1. Beneficial effects were noted when extracellular HMGB1 expression was low, while severe inflammation coincided with substantial extracellular synovial HMGB1 expression.. Therapeutic compounds like oxaliplatin and gold salts share a capacity to inhibit nuclear HMGB1 release and to ameliorate the course of synovial inflammation. These observations support the hypothesis that HMGB1 plays an important functional role in the pathogenesis of arthritis and may represent a novel target molecule for therapy.

Topics: Animals; Arthritis, Experimental; Cartilage, Articular; Cell Nucleus; Cell Proliferation; Cells, Cultured; Collagen Type II; HMGB1 Protein; Injections, Intraperitoneal; Lymph Nodes; Macrophages; Mice; Mice, Inbred DBA; Organoplatinum Compounds; Ovalbumin; Oxaliplatin; Synovitis; T-Lymphocytes; Time Factors; Tissue Distribution

Fibrin deposits adhered to the synovial surface are typical of rheumatoid joints. Since fibrin appears to have a role in arthritis perpetuation our aim was to investigate how these deposits are formed and the consequences of their adhesion to the tissue.. The appearance of fibrin aggregates either free in the synovial fluid or attached to the membrane was studied in rabbits with antigen-induced arthritis by histological techniques at different time points from challenge. In the fixed synovial membranes areas of fibrin-bound synovium were evaluated by qualitative variables to obtain a sequential profile of morphological changes.. Fibrin aggregates appeared from the initial stages of the disease in the synovial effusion. Later on, they were localized on the synovial surface and progressive changes were noted at the fibrin-tissue interface, ending with the invasion of the aggregates by synovial cells and their incorporation into the tissue.. Fibrin aggregates generated inside the joint cavity may constitute a source of activation and acquisition of invasiveness of the synovial fibroblasts, a process to explore within the perpetuating mechanisms of rheumatoid arthritis.

Topics: Animals; Arthritis, Rheumatoid; Fibrin; Fibrinogen; Fibroblasts; Fibronectins; Hindlimb; Immunohistochemistry; Models, Animal; Ovalbumin; Rabbits; Synovial Fluid; Synovial Membrane; Synovitis; Time Factors; Tissue Adhesions

Chronic synovitis was induced in seven sheep and nine pigs to investigate the potential applicability of laser treatment in arthroscopic synovectomy. Systemic sensitization was accomplished using chicken egg or turkey egg albumin antigens with Freund's incomplete adjuvant, enriched with killed and dried Mycobacterium tuberculosis. Ten days after the second immunizing dose, skin sensitization testing was undertaken. After a satisfactory systemic reaction had been observed, the respective antigen was injected once or twice into the left knee of each animal at 2-week intervals. After chicken egg albumin sensitization at varying systemic immunization and joint injection doses, sheep (five of five) showed neither strong morphologic nor continuous synovitis, despite a positive systemic reaction. In pigs (three of three) the inflammatory signs also were unsatisfactory for the manifestation and characterization of a synovitis model. In contrast, the application of turkey egg albumin to pigs (six of six) during the 4-month study provided a persistent, clearly manifested synovitis that developed visible villi formation and an amber to gray synovial fluid and microscopically showed follicular aggregations of lymphocytes and plasma cells. In similarly immunized sheep (two of two), only a light synovitis developed with occasional perivascular inflammatory foci.

Topics: Animals; Antigens; Antigens, Bacterial; Arthroscopy; Chickens; Chronic Disease; Disease Models, Animal; Endoscopy; Freund's Adjuvant; Hindlimb; Immunization; Injections, Intra-Articular; Laser Therapy; Lymphocytes; Mycobacterium tuberculosis; Ovalbumin; Plasma Cells; Sheep; Swine; Synovial Fluid; Synovitis; Turkeys

Minimally invasive synovectomy techniques have been unsuccessful due to lack of selectivity. The purpose of this study was to evaluate the potential of photodynamic therapy to destroy diseased synovium in an antigen-induced arthritis model.. Three sets of experiments evaluated the biodistribution and treatment effects of Photofrin (PF) in rabbits with bilateral knee antigen-induced arthritis. The first set of experiments evaluated the biodistribution of PF in articular tissues of 30 rabbits from 6-72 hours after systemic injection of 2 mg/kg. In the second series of experiments, light was delivered to the knee joint via cleaved optical fibers, whereas for the third, light was delivered via a 600 microm diffusion tip fiber. Tissues were harvested at 2 and 4 weeks posttreatment.. The biodistribution experiments demonstrated maximal uptake in inflamed synovium at 48 hours and a lack of uptake in normal tissues. With bare cleaved fibers, necrosis was observed in one specimen at 2 weeks and was absent in all specimens at 4 weeks. In the third experiment, synovial necrosis was observed in 3 of 7 specimens at 2 weeks and 3 of 8 at 4 weeks. No damage to articular cartilage or periarticular tissues was seen with either mode of light delivery.. These studies indicate that selective destruction of synovium can be achieved with PF and suggest that optimization of light delivery techniques will play an important role in development of this new technique.

Topics: Analysis of Variance; Animals; Arthritis, Rheumatoid; Cartilage, Articular; Dihematoporphyrin Ether; Disease Models, Animal; Hyperplasia; Knee Joint; Microscopy, Fluorescence; Necrosis; Ovalbumin; Photochemotherapy; Rabbits; Synovial Membrane; Synovitis

Children with juvenile rheumatoid arthritis or juvenile chronic arthritis often exhibit temporomandibular joint (TMJ) involvement accompanied by pain, dysfunction, and growth abnormalities. Despite the severe functional and developmental consequences of this disease, its pathogenesis remains poorly understood, but important insights may be provided by a suitable animal model of this disease. The purpose of this study was to develop and histologically characterize a juvenile animal model of antigen-induced arthritis of the TMJ. Arthritis was induced with an intra-articular administration of ovalbumin in previously sensitized 10-week-old male New Zealand white rabbits. Sham-treated and untreated rabbits were used as controls. The TMJs were retrieved en bloc at 5, 10, 15, 35, and 55 days post-challenge for histology and matrix histochemistry. Antigen-treated joints demonstrated severe arthritis, including mononuclear cell infiltration, synovial lining and villous hyperplasia, and pannus formation, as early as 5 days after challenge; the arthritis was maintained up to 55 days post-challenge. A decrease in the area of the TMJ disc that stained positively for glycosaminoglycans was observed throughout the experimental period. Loss of collagen staining was primarily localized to sites at the junction of the synovium with bone and fibrocartilage. The histopathologic features of this model of antigen-induced arthritis of the juvenile rabbit TMJ are similar to those observed previously in adult animal models of experimental arthritis and in human rheumatoid arthritis. This animal model will be useful for understanding the pathogenesis of juvenile rheumatoid arthritis of the TMJ, and for exploring the mechanisms for aberrant craniofacial growth.

Topics: Analysis of Variance; Animals; Arthritis, Experimental; Arthritis, Juvenile; Cartilage, Articular; Collagen; Coloring Agents; Disease Models, Animal; Extracellular Matrix Proteins; Glycosaminoglycans; Histocytochemistry; Male; Ovalbumin; Phenazines; Rabbits; Synovial Membrane; Synovitis; Temporomandibular Joint Disorders

The distribution of the matrix metalloproteinases, collagenase, stromelysin, gelatinases A and B, and the tissue inhibitor of metalloproteinases in cartilage and synovium removed from rabbits up to 27 days after induction of two models of arthritis was investigated by immunolocalization. Following intra-articular injection of poly-D-lysine/hyaluronic acid coacervate, collagenase and stromelysin were found bound to cartilage matrix, but there was little increase in chondrocyte synthesis of these enzymes. The synovium underwent a complex wound healing response involving invagination and encapsulation of the coacervate and inflammatory cell debris, during which all four metalloproteinases and tissue inhibitor of metalloproteinase could be immunolocalized. The second model, intra-articular injection of ovalbumin into sensitized rabbits, caused considerable chondrocyte necrosis; collagenase was found bound to cartilage matrix on day 13, although again there was little evidence of synthesis by chondrocytes. Inflammatory cell infiltration of meniscoid synovia took place initially, followed by fibrosis involving macrophagelike cells secreting gelatinase A. In both models there was rapid loss of glycosaminoglycan metachromasia from the cartilage matrix. These results are discussed in relation to current knowledge of metalloproteinase involvement in the chronic rheumatoid synovial pannus erosion of cartilage in humans. The data suggest that there are considerable differences between rheumatoid arthritis and these models, and their use must therefore be carefully defined.

Topics: Animals; Arthritis, Experimental; Cartilage; Fluorescent Antibody Technique; Hyaluronic Acid; Metalloendopeptidases; Neoplasm Proteins; Ovalbumin; Polylysine; Rabbits; Synovitis; Tissue Inhibitor of Metalloproteinase-2

A rat model has been developed to examine the possible role of homocytotropic antibodies in initiating or exacerbating synovial inflammation. The technique, passive synovial anaphylaxis, involves passively sensitizing rat knee joints with specific IgE, then challenging intravenously with the corresponding antigen while monitoring for signs of inflammation. Swelling of the sensitized joints reached maximum 2 h after the challenge, then gradually decreased to prechallenge levels by 24 h. Radioisotopic joint scans detected a passive synovial anaphylaxis induced increase in local blood flow and exudation within the joints. The degree of swelling correlated directly with the amount of antigen specific IgE in the sensitizing serum, and individual joints remained sensitized for up to 36 days after the IgE injection.

Topics: Animals; Antibody Formation; Dinitrophenols; Enzyme-Linked Immunosorbent Assay; Hypersensitivity; Immunoglobulin E; Knee Joint; Ovalbumin; Rats; Rats, Inbred BN; Rats, Inbred Strains; Serum Albumin, Bovine; Synovitis; Time Factors; Whooping Cough

The relative contributions of cellular and humoral immunity to cartilage destruction in chronic arthritis has been investigated in a model of chronic synovitis in the rabbit. In this model, antigen-induced arthritis, immunization with ovalbumin in Freund's complete adjuvant (FCA) followed by intra-articular injection of this protein produces a chronic synovitis associated with loss of proteoglycan from articular cartilage. In addition, the synovial lining cell population is metabolically activated. Similar treatment of animals immunized with ovalbumin in Freund's incomplete adjuvant (FIA) produced a resolving arthritis which initially (over the first 7 days) appears to be identical to that in FCA-immunized animals, apart from the lack of activation of synovial lining cells. Following this initial synovitis the joints return to apparent normality apart from a persistent 'low grade' synovitis consisting mainly of a plasma cell infiltrate. The most striking finding in the FIA-immunized animals is the rapid loss (greater than 30% by day 7) and recovery of proteoglycan from the matrix of articular cartilage. These findings show that the perpetuation of chronic destructive synovitis in the rabbit requires the presence of active cellular immunity.

Topics: Acid Phosphatase; Animals; Antibodies; Arthritis; Arthritis, Experimental; Cartilage, Articular; Female; Guinea Pigs; Hypersensitivity, Delayed; Immunity, Cellular; Male; Ovalbumin; Proteoglycans; Rabbits; Synovial Fluid; Synovitis

The much favoured ovalbumin antigen induced model of arthritis in rabbits is widely used in rheumatoid arthritis (RA) research. When examined histologically, it was found to have important deficiencies as parallels to the human disease. After sensitization to ovalbumin, 2 intraarticular challenge doses of a magnitude at each end of the spectrum used by investigators were used in 152 rabbits. The effects of the high and low dose challenges were examined histologically with particular attention to the articular cartilage. With high doses, the gross and histological changes in the knee joint were remarkably akin to acute cartilage necrosis rather than RA1. In the low dose, a milder smoldering arthritis was produced. These observations suggest that, depending on the challenge dose used, there is a tremendous variability in the kind of arthritis produced by the antigen induced arthritis model. Furthermore, it is suggested that previous conclusions about the pathophysiology and immunology of RA drawn from the models that produce a rapid and severe arthritis should be reexamined.

Topics: Animals; Antigens; Arthritis, Rheumatoid; Cartilage; Disease Models, Animal; Evaluation Studies as Topic; Female; Immunization; Inflammation; Injections, Intra-Articular; Lipid Metabolism; Male; Ovalbumin; Rabbits; Research Design; Synovitis

Acute experimental synovitis was produced by intra-articular challenge of 3 baboons (Papio cynocephalus) sensitised with ovalbumin. Haemagglutination tests revealed high titres of circulating antiovalbumin antibody. Measurements were made of articular diameter, circumference, and temperature before the animals were killed on days 1, 5, and 20. The sterile synovitis was investigated microscopically and by immunoperoxidase methods. IgG, IgM, IgA, C3, and fibrin were identified within the synovial membranes which were extensively infiltrated with plasmacytes and other mononuclear cells. It was concluded that the baboon can respond to exogenous antigen histologically in a manner analogous to that of nonprimates. Some features of the response recall those of the synovitis of active human rheumatoid disease.

Topics: Animals; Antigens; Hemagglutinins; Immunoenzyme Techniques; Immunoglobulin G; Ovalbumin; Papio; Synovial Membrane; Synovitis

Fibronectin (FN), a high molecular weight glycoprotein, is present in plasma and is a normal structural component of the synovium in the rabbit, as it is in man. FN is also involved in the sequence of changes seen in synovium in experimental antigen-induced arthritis. Its widespread distribution in inflamed synovia in the initial acute phase of induced arthritis probably merely reflects the presence of FN of plasma origin in serous exudates. In established experimental arthritis, FN co-distributes with fibrin, while in synovia undergoing organisation, FN is present intracellularly in several types of mesenchymal cells (suggesting local synthesis) and is deposited on immature collagen fibrils. However, it is no longer present when mature collagen is formed. The persistence of FN, along with fibrin, in inflamed joints, and its involvement in fibrosis, suggest that it may play a significant part in determining the chronicity of this form of experimental arthritis.

Topics: Animals; Antigens; Arthritis; Fibronectins; Fluorescent Antibody Technique; Ovalbumin; Rabbits; Synovial Membrane; Synovitis

Topics: Animals; Arthritis, Rheumatoid; Chronic Disease; Disease Models, Animal; Glycosaminoglycans; Injections, Intra-Articular; Ovalbumin; Rabbits; Species Specificity; Swine; Synovitis

Topics: Animals; Antigens; Arthritis, Rheumatoid; Disease Models, Animal; Fluorouracil; Freund's Adjuvant; Hindlimb; Injections, Intra-Articular; Ovalbumin; Rabbits; Synovial Membrane; Synovitis; Time Factors

In an experimental arthritis induced by injection of bovine serum albumin or egg albumin into the joints of previously immunized animals, it has been demonstrated that the major portion of the radioactively labeled antigens injected was localized to avascular collagenous tissues in the joint, i.e., articular cartilage, menisci, and intra-articular ligaments. The antigens were partially eluted from the tissues with 5 M guanidine solution, but not with acid buffers or by 3 M magnesium chloride. The radioactive material eluted with guanidine was at least 80% precipitable by specific antisera. The radioactively labeled-inducing antigen was identified on the surface of articular collagenous tissues from arthritic joints by radioautography and immunofluorescence. Rabbit immunoglobulin and C3 were demonstrated in the same sites by immunofluorescence. The presence of specific antibody in collagenous tissues was demonstrated by the selective in vitro binding of (125)I-labeled-inducing antigen to menisci from arthritic joints of immunized animals. The evidence obtained indicates that in this model of chronic arthritis, the inducing antigen persists for long periods of time in the form of immune complexes in the surface layers of the intra-articular collagenous tissue. The antigen retained in this form may be responsible for the chronicity of the synovitis by serving as a direct stimulus for the maintenance of prolonged antibody synthesis in the synovium and by providing a source of complement-fixing antigen-antibody complexes for the mediation of joint inflammation.

Topics: Animals; Antibody Formation; Antigen-Antibody Complex; Antigens; Arthritis; Autoradiography; Cartilage, Articular; Chronic Disease; Collagen; Complement System Proteins; Disease Models, Animal; Fluorescent Antibody Technique; Guanidines; Immunoglobulins; Inflammation; Iodine Isotopes; Knee Joint; Ovalbumin; Rabbits; Serum Albumin, Bovine; Synovial Membrane; Synovitis

Topics: Animals; Antigens; Arthritis; Autoradiography; Binding Sites; Chromatography, DEAE-Cellulose; Female; Immunoelectrophoresis; Immunoglobulin G; In Vitro Techniques; Injections, Intra-Articular; Iodine Isotopes; Macrophages; Ovalbumin; Rabbits; Synovial Fluid; Synovitis

Topics: Animals; Antibody Formation; Antibody-Producing Cells; Antigens; Autoradiography; Fluorescent Antibody Technique; Intestines; Knee Joint; Liver; Lymph Nodes; Macrophages; Microscopy, Electron; Ovalbumin; Plasma Cells; Rabbits; Spleen; Synovial Membrane; Synovitis; Thymidine; Tritium

Topics: Animals; Arthritis; Cartilage, Articular; Chronic Disease; Disease Models, Animal; Female; Hindlimb; Leukocytes; Lymphocytes; Macrophages; Male; Ovalbumin; Prednisolone; Rabbits; Synovitis

Topics: Animals; Antigens; Hindlimb; Hypersensitivity, Delayed; Injections, Intra-Articular; Iodine Isotopes; Ovalbumin; Rabbits; Synovial Membrane; Synovitis

Topics: Amino Acids; Animals; Antibody Formation; Antigens; Carbon Isotopes; Chromatography; Culture Techniques; Goats; Immune Sera; Immunodiffusion; Immunoelectrophoresis; Lectins; Ovalbumin; Rabbits; Serum Albumin, Bovine; Spectrophotometry; Spleen; Streptolysins; Synovial Membrane; Synovitis

Topics: Animals; Antigen-Antibody Reactions; Arthus Reaction; Chloroquine; Cortisone; Endotoxins; Models, Biological; Ovalbumin; Phenylbutazone; Rabbits; Sodium Salicylate; Synovitis