fibrin and Synovitis

Intracavitary fibrin clots may initiate pannus formation and the immunopathology of RA. Two critical steps, probably host dependent, may determine the development of RA: an altered regulation of extravascular haemostasis or an aberrant reactivity of synovial fibroblasts to the adhered fibrin clots. Current treatments for RA target events downstream of fibrin deposition, perhaps agents acting at an earlier stage should be tried.

Topics: Arthritis, Rheumatoid; Blood Coagulation Disorders; Fibrin; Fibrinolysis; Humans; Synovitis

Topics: Arthritis, Rheumatoid; Connective Tissue; Fibrin; Humans; Necrosis; Rheumatoid Factor; Rheumatoid Nodule; Synovitis; Wounds and Injuries

Topics: Animals; Antigens; Arthritis, Rheumatoid; Autoimmune Diseases; Cartilage; Cattle; Cell Membrane Permeability; Densitometry; Esterases; Fibrin; Fibrinolysis; Histocytochemistry; Humans; Hyaluronoglucosaminidase; Hydrocortisone; Inflammation; Kinins; Leukocytes; Lysosomes; Mice; Microscopy, Electron; Neuraminidase; Oxidation-Reduction; Peptide Hydrolases; Phagocytosis; Phosphoric Monoester Hydrolases; Pinocytosis; Proteins; Rabbits; Rats; Rheumatic Diseases; Synovial Membrane; Synovitis

To evaluate the influence of impaired masseter function during growth on the development of temporomandibular synovitis.. Sixteen 3-week-old male Wistar rats were classified into four groups. The first group served as control; and in the second group, jaw opening was forced for 3 hours when the rats were 9 weeks old. In the third and fourth groups, the masseter muscles were bilaterally resected at 3 weeks of age, and the rats in the fourth group were additionally forced to open their jaw at 9 weeks of age. All rats were sacrificed at 9 weeks. Temporomandibular joint (TMJ) tissue samples were processed for histology, and evaluated for cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions by immunohistochemistry to examine the inflammatory changes in the synovial membrane.. The control group showed noninflammatory changes. In the jaw-opening group, vascular dilation and weak COX-2 immunoreactivity were induced by jaw opening in the synovium. In the masseter-resection group, the masseter-resected rats exhibited moderate synovial changes while in the resection with opening group, the masseter-resected rats revealed more significant inflammatory changes including synovial hyperplasia, dilated vasculature, fibrin deposits, and intense immunoreactivity for COX-2 and iNOS, all caused by jaw opening.. These results suggest that masseter activity in the growth period is an important factor in the induction of temporomandibular synovitis.

Topics: Animals; Cyclooxygenase 2; Dilatation, Pathologic; Fibrin; Hyperplasia; Immunohistochemistry; Male; Masseter Muscle; Muscle Weakness; Nitric Oxide Synthase Type II; Range of Motion, Articular; Rats; Rats, Wistar; Stress, Mechanical; Synovial Membrane; Synovitis; Temporomandibular Joint; Temporomandibular Joint Disorders; Vascular Diseases

C4b-binding protein (C4BP) is a plasma oligomeric glycoprotein that participates in the regulation of complement and haemostasis. Complement-regulatory activity depends on the C4BPalpha-polypeptide, whereas the C4BPbeta-polypeptide inactivates protein S, interfering with the anti-coagulatory protein C-dependent pathway.. To investigate the expression of C4BPbeta in the rheumatoid joint.. Expression of C4BP was studied in synovial explants from patients with rheumatoid arthritis, osteoarthritis and healthy controls, using immunohistochemistry and in situ hybridisation. C4BP isoforms and free C4BPbeta were studied in synovial effusions from patients with rheumatoid arthritis, osteoarthritis and microcrystalline arthritis (MCA) by immunoblotting; total and free protein S levels were studied by enzyme immunoassay.. C4BPbeta was overexpressed in the synovial membranes of patients with rheumatoid arthritis, in close association with the severity of synovitis and the extension of interstitial fibrin deposits. As many as 85% fluids from patients with rheumatoid arthritis contained free C4BPbeta, whereas this unusual polypeptide was present in 50% fluids from patients with MCA and 40% fluids from patients with osteoarthritis. Free protein S at the effusions was pathologically reduced in patients with rheumatoid arthritis and MCA, and remained normal in patients with osteoarthritis.. C4BPbeta is expressed by the inflamed synovial tissue, where it can participate in processes of tissue remodelling associated with invasive growth.

Topics: Adult; Arthritis; Arthritis, Rheumatoid; Complement C4b-Binding Protein; Fibrin; Histocompatibility Antigens; Humans; Immunoenzyme Techniques; Osteoarthritis, Knee; Protein Isoforms; Protein S; Synovial Fluid; Synovial Membrane; Synovitis

Autoantibodies to deiminated (citrullinated) proteins are the most specific serological markers of rheumatoid arthritis (RA). Deimination is critical in generating the peptidic epitopes they recognize. In the synovial tissue (ST), deiminated forms of the alpha- and beta-chains of fibrin are their major autoantigenic targets (anti-human fibrin(ogen) autoantibodies (AhFibA)). We investigated whether the presence of deiminated fibrin in the ST was specific for RA, because this could explain why AhFibA are RA specific. In 13 patients with RA and 19 patients with various other rheumatological disorders, knee ST biopsies were collected in macroscopically inflamed areas identified under arthroscopy. Synovitis was histopathologically confirmed in all of the biopsies. By immunoblotting, using antisera to fibrin, Abs to citrullyl residues, and AhFibA purified from RA sera, deiminated fibrin was evidenced in ST extracts from all of the patients. Moreover, variations in the degree of fibrin deimination were observed that were not related to the disease. Immunohistochemical analysis, using Abs to citrullyl residues and an antiserum to fibrin on adjacent serial sections of ST, confirmed the results because deiminated proteins colocalized with fibrin in RA as well as in control patients. Therefore, fibrin deimination in the ST is a general phenomenon associated to any synovitis, which does not necessarily induce a B autoimmune response with production of AhFibA.

Topics: Adult; Aged; Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Case-Control Studies; Citrulline; Epitopes; Female; Fibrin; Humans; Male; Middle Aged; Models, Immunological; Synovial Membrane; Synovitis

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

Electron microscopy was used to examine the histologic effect of trauma on the rat temporomandibular joint synovial membrane.. Trauma to the TMJ in male Wister rats (100-200 g) was introduced through repeated forced condylar hypermobility. Ultrastructural observations were made 5 days and 6 weeks after the trauma.. The early response of the synovial membrane was synovial hyperplasia, type A synovial cell loss, dilation of the r-ER in the type B synovial cells and fibrin deposition on the synovial surfaces. The late response included degeneration of synovial cells with swollen mitochondria and cell projections, and cell fragmentation. Large amount of fibrin deposition on opposing surface layers was also noticed.. The type A cell loss and fibrin deposition followed by the occurrence of fibrinous materials at opposing surface layers of the synovial membrane suggest that traumatic synovitis causes synovial adhesions.

Topics: Animals; Endoplasmic Reticulum, Rough; Fibrillar Collagens; Fibrin; Hyperplasia; Joint Instability; Male; Rats; Rats, Wistar; Synovial Membrane; Synovitis; Temporomandibular Joint; Tissue Adhesions

Clinical and experimental evidence suggests that extravascular fibrin deposition in arthritic joints is prominent and deleterious. The aim of this study was to investigate the contributions of tissue factor (TF) and its inhibitor, TF pathway inhibitor (TFPI), in arthritis.. Synovial tissue specimens obtained from 10 patients with rheumatoid arthritis (RA) and 12 patients with osteoarthritis (OA) were scored histologically for inflammation and fibrin content. TF and TFPI levels were assayed at antigenic and functional levels. TF messenger RNA (mRNA) levels were determined using RNase protection assays. The effect of TF inhibition in murine antigen-induced arthritis (AIA) was assessed by administering systemically active site-blocked activated factor VIIa (FVIIai).. Functional TF activity was significantly increased in synovial membranes from RA patients compared with those from OA patients. In contrast, no difference in TF mRNA and TF antigenic levels was observed between these 2 groups. This discrepancy can be accounted for by TFPI, because we observed a negative correlation between TF activity and TFPI activity. There was a significant difference between the RA and OA groups in terms of synovial inflammation, with more inflammation observed in the RA group. Most importantly, TF activity was associated with fibrin (P = 0.024) and with histologic inflammation (P = 0.03) scores. In AIA, inhibition of TF-induced coagulation by FVIIai led, on day 9 of arthritis, to decreased synovial thickness and decreased articular cartilage damage, although only the latter difference between controls and treated mice reached significance (P < 0.04). Finally, in FVIIai-treated mice, there was a strong negative association between the prothrombin time and intraarticular fibrin deposition.. Our results show that TF expression in arthritic synovial tissue favors extravascular coagulation and may play a role in inflammation in RA. In this context, TF inhibitors may be of therapeutic value.

Topics: Aged; Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Dansyl Compounds; Disease Models, Animal; Factor VIIa; Female; Fibrin; Fibrinolytic Agents; Hindlimb; Humans; Immunohistochemistry; Lipoproteins; Male; Mice; Mice, Inbred C57BL; Middle Aged; Osteoarthritis; Radionuclide Imaging; RNA, Messenger; Synovitis; Thromboplastin

We evaluated histologically samples of synovial tissue from the knees of 50 patients with rheumatoid arthritis (RA). The samples were taken during revision for aseptic loosening. The findings were compared with those in 64 knees with osteoarthritis (OA) and aseptic loosening and in 18 knees with RA without loosening. The last group had been revised because of failure of the inlay or the coupling system of a constrained prosthesis. All the patients had had a total ventral synovectomy before implantation of the primary prosthesis. In all three groups a foreign-body reaction and lymphocellular infiltration were seen in more than 80% of the tissue samples. Deposits of fibrin were observed in about one-third to one-half of the knees in all groups. Typical signs of the reactivation of RA such as rheumatoid necrosis and/or proliferation of synovial stromal cells were found in 26% of knees with RA and loosening, but not in those with OA and loosening and in those with RA without loosening. Our findings show that reactivation of rheumatoid synovitis occurs after total knee replacement and may be a cofactor in aseptic loosening in patients with RA.

Topics: Aged; Arthritis, Rheumatoid; Female; Fibrin; Foreign-Body Reaction; Humans; Knee Prosthesis; Lymphocytes; Male; Middle Aged; Osteoarthritis; Prosthesis Failure; Recurrence; Reoperation; Synovitis

To determine the effect of the thrombin inhibitor, hirudin, on the pathogenesis of murine antigen induced arthritis (AIA).. AIA was induced by intra-articular injection of methylated bovine serum albumin in the knee joints of previously immunised mice. Hirudin (injected subcutaneously 3 x 200 microg/mouse/day) was given over 13 days, starting three days before arthritis onset, and its anticoagulant effect monitored by clotting times. Arthritis severity was evaluated by technetium-99m ((99m)Tc) uptake in the knee joints and by histological scoring. In addition, intra-articular fibrin deposition was examined by immunohistochemistry, and synovial cytokine mRNA expression measured by RNase protection.. Joint inflammation, measured by (99m)Tc uptake, was significantly reduced in hirudin treated mice at days 7 and 10 after arthritis onset. Histologically, synovial thickness was markedly decreased in hirudin treated mice compared with untreated ones. By contrast, no difference in articular cartilage proteoglycan content was found between both groups. Intra-articular fibrin deposition and synovial interleukin 1beta mRNA levels, were slightly reduced ( approximately 20%) in arthritic joints from hirudin treated mice compared with untreated ones at day 10 of AIA.. Hirudin reduces joint inflammation associated with AIA by fibrin-dependent and independent mechanisms.

Topics: Animals; Antithrombins; Arthritis, Rheumatoid; Cytokines; Drug Evaluation, Preclinical; Fibrin; Hirudin Therapy; Interleukin-1; Mice; Mice, Inbred C57BL; Proteoglycans; Severity of Illness Index; Synovitis; Technetium; Treatment Outcome

Holmium-laser synovectomy was carried out to remove allergically inflamed synovial membranes in rabbit knee joints. The healing process was then investigated at different periods. Left knee joints of 12 rabbits were exposed to Ho:YAG-laser radiation at a wavelength of 2.1 microns, pulse energy of 600 mJ, pulse length of 1 ms, and repetition rate of 3 Hz. Twelve others were treated conventionally and 12 served as controls. After 1 day, 1 week, and 1 and 3 months, respectively, 3 animals from each group were sacrificed and the synovialis grossly and microscopically examined. Coagulation necrosis, inflammation, and edema resulted following laser therapy. After 1 week, the synovial layer consisted of a scarlike formation of fibers and within 1 month, its surface appeared smooth. The mechanical abrasion caused hemorrhage and necrosis. Fibrosis developed in the capsular layers, and after 3 months, the surface appeared coarse and villous. Based on these preliminary findings, holmium-laser synovectomy may offer an alternative method to existing therapeutic techniques.

Topics: Aluminum Silicates; Animals; Arthritis, Experimental; Collagen; Curettage; Edema; Fibrin; Granulocytes; Histiocytes; Holmium; Knee Joint; Light Coagulation; Macrophages; Necrosis; Rabbits; Synovectomy; Synovial Fluid; Synovial Membrane; Synovitis; Yttrium

Synovial biopsies were obtained from 28 patients with various kinds of chronic arthritis, at synovectomy and 6 and 12 months later. The tissues were examined by immunofluorescence technique, recording the quantities of cells and extracellular deposits staining with polyclonal antisera to IgG, IgA, IgM, C3c, fibrinogen, and chi and lambda light chains, and monoclonal antibodies to CD3, CD5, CD11b, HLA DR, and TCC (Terminal Complement Complex). These parameters were compared with scores obtained by arthroscopy and clinical evaluation (Colorado Knee Score) performed at the same time. Taken as a group, the immunological parameters showed reduction in activity 6 months after synovectomy (p less than 0.01), and a tendency to revert to base-line values after 12 months. A similar reduction in activity after 6 months was also found by arthroscopic and clinical evaluation. Thus, this longitudinal study demonstrated a relationship between changes in immunologic activity, arthroscopic findings and clinical activity after synovectomy in patients with chronic arthritis. This is consistent with an immunological pathogenesis for the inflammation in these joints.

Topics: Adolescent; Adult; Antigens, CD; Arthritis, Juvenile; Arthritis, Psoriatic; Arthritis, Rheumatoid; Arthroscopy; Child; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique; HLA-DR Antigens; Humans; Immunoglobulins; Male; Middle Aged; Prospective Studies; Synovectomy; Synovial Membrane; Synovitis

Scanning electron microscopy has been used to study experimental antigen induced arthritis, providing a unique perspective of the early inflammatory events. An initial aggregation of acute inflammatory cells was noted at the synovial-meniscal junction with maximal numbers observed between 12 and 24 h post challenge. Variations in cell surface ruffling, which may represent different phases of activation, were observed throughout the Arthus response. By 48 h post challenge the meniscal and synovial surfaces were covered by a mat of fibrin and degraded cell remnants.

Topics: Animals; Arthus Reaction; Cell Membrane; Female; Fibrin; Immunization; Inflammation; Male; Menisci, Tibial; Microscopy, Electron, Scanning; Neutrophils; Rabbits; Serum Albumin, Bovine; Synovial Membrane; Synovitis

Owing to special reactivity anchored in its structure the connective tissue responds to all kinds of injuries with tissue changes which in their completeness are designated as inflammation. An expressive carrier of mesodermal inflammation is the synovial membrane in which these tissue changes are manifested at first by the vessels and cells of the blood, and subsequently by all other constituents of the synovial membrane.

Topics: Collagen; Fibrin; Fibroblasts; Humans; Hypertrophy; Inflammation; Necrosis; Synovial Membrane; Synovitis; Time Factors

In the early stage of rheumatoid synovitis, changes in synoviocytes of the cover layer in the joints with clinical manifestations of arthritis differ from stereotype reactions of these cells in the advanced stage of the disease. Fibrin, IgG and C3-fraction of complement are found on the surface and in the depth of the cover layer. Light and electron microscopy revealed the features of type B synoviocytes prevalent in the cover layer in the early stage of the disease: polymorphism and rounding of the nuclei of synoviocytes, mitoses, fragmentation and degeneration of the nucleolus, loosening of the chromatin network and appearance of interchromatin granules, nuclear bodies, formation of multinucleated synoviocytes and symplasts, destruction of organelles, activation of lysosomal apparatus of the cells. These changes may be interpreted as simultaneous manifestations of cell activation and cytopathologic effect. They are likely to be due to the effect of the etiological factor and immunocomplex mechanism. The detection of dystrophically altered chrondrocytes in the cover layer confirms the opinion of simultaneous participation of the synovial and cartilage components of the joint in the rheumatoid process.

Topics: Adult; Arthritis, Rheumatoid; Biopsy, Needle; Complement C3; Female; Fibrin; Humans; Immunochemistry; Immunoglobulin G; Male; Microscopy, Electron; Middle Aged; Synovial Membrane; Synovitis; Time Factors

Desmosomes or desmosome-like structures do not occur between normal synovial cells but such structures do develop between the synovial cells in cases of traumatic arthritis, rheumatoid arthritis and villonodular synovitis. Morphological evidence is presented suggesting that such structures develop as a result of the interaction of fibrin trapped between synovial cells and the plasmamembrane of these cells.

Topics: Arthritis, Rheumatoid; Desmosomes; Fibrin; Humans; Synovial Membrane; Synovitis

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Cell Count; Fibrin; Humans; Proteoglycans; Synovial Fluid; Synovial Membrane; Synovitis

Topics: Adolescent; Adult; Arthritis; Arthritis, Rheumatoid; Biopsy; Child; Diagnosis, Differential; Female; Fibrin; Follow-Up Studies; Histocytochemistry; Humans; Knee; Knee Joint; Male; Middle Aged; Prognosis; Retrospective Studies; Rheumatoid Factor; Synovial Membrane; Synovitis

Topics: Agar; Animals; Animals, Newborn; Carpal Bones; Cattle; Cattle Diseases; Edema; Fibrin; Histological Techniques; Inflammation; Injections, Intra-Articular; Joints; Mycoplasma; Mycoplasma mycoides; Radius; Synovial Fluid; Synovitis; Tarsal Joints; Time Factors

Topics: Animals; Connective Tissue; Female; Fibrin; Freund's Adjuvant; Knee Joint; Macrophages; Male; Osmium; Oxides; Plasma Cells; Rabbits; Synovial Membrane; Synovitis

Topics: Arthritis, Rheumatoid; Chronic Disease; Fibrin; Humans; Inflammation; Microscopy, Electron; Necrosis; Synovial Membrane; Synovitis

Topics: Adjuvants, Immunologic; Animals; Antibodies; Antigens; Arthritis, Rheumatoid; Autoimmune Diseases; Chronic Disease; Fibrin; Gout; Humans; Hypersensitivity, Delayed; Inflammation; Joints; Macrophages; Mycobacterium tuberculosis; Plasma Cells; Polysaccharides; Rabbits; Synovitis; Uric Acid