acid-phosphatase and Gout

To analyze cellular mechanisms of bone erosion in gout.. Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) from patients with gout were analyzed for the presence of osteoclast precursors. Fixed tophus and bone samples were analyzed by immunohistochemistry. Mechanisms of osteoclastogenesis were studied by culturing murine preosteoclast RAW 264.7 cells, bone marrow stromal ST2 cells, and human synovial fibroblasts with monosodium urate monohydrate (MSU) crystals.. PBMCs from patients with severe erosive gout had the preferential ability to form osteoclast-like cells in culture with RANKL and monocyte colony-stimulating factor (M-CSF). The number of PBMC-derived tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells strongly correlated with the number of tophi (r = 0.6296, P = 0.630). Patients with severe erosive and tophaceous gout also had higher circulating concentrations of RANKL and M-CSF. Furthermore, greater numbers of TRAP-positive multinucleated cells were cultured from SFMCs derived from gouty knee effusions than from paired PBMCs (P = 0.004). Immunohistochemical analysis demonstrated numerous multinucleated cells expressing osteoclast markers within tophi and at the interface between soft tissue and bone. MSU crystals did not directly promote osteoclast formation from RAW 264.7 cells in vitro. However, MSU crystals inhibited osteoprotegerin gene and protein expression in ST2 cells and human synovial fibroblasts, without significantly altering RANKL gene expression. Conditioned medium from ST2 cells cultured with MSU crystals promoted osteoclast formation from RAW 264.7 cells in the presence of RANKL.. Chronic tophaceous and erosive gout is characterized by enhanced osteoclast development. These data provide a rationale for the study of osteoclast-targeted therapies for the prevention of bone damage in chronic gout.

Topics: Acid Phosphatase; Animals; Bone Resorption; Cell Differentiation; Cell Line; Cohort Studies; Fibroblasts; Gout; Humans; Isoenzymes; Male; Mice; Middle Aged; Monocytes; Osteoclasts; Stromal Cells; Synovial Fluid; Tartrate-Resistant Acid Phosphatase; Uric Acid

Topics: Acid Phosphatase; Arthritis, Rheumatoid; Gout; Histocytochemistry; Humans; L-Lactate Dehydrogenase; Mitochondria; Rheumatic Nodule; Succinate Dehydrogenase; Synovial Fluid; Synovial Membrane; Thiosulfate Sulfurtransferase; Ubiquinone

This paper describes a morphologic, quantitative, cytochemical study of mononuclear non lymphoid cells in knee synovial fluid in osteoarthritis and various arthritides. Morphologic criteria allow to identify among these cells various synoviocytic and monocytic subtypes with in both types, phagocytic subtypes. Quantitative study shows in arthritides an important afflux of monocytes and a hyperexfoliation of synoviocytes. In fluids with intermediate cellularity, Monocytes/Synoviocytes ratio allows the differential cytodiagnosis between osteoarthrosis and arthritis. All monocytic subtypes and especially the phagocytic one are highly significantly increased in arthritides. Synoviocytic subtypes show a lower increase, except the phagocytic one, which is not changed. Giant multinuclear synoviocytes are found in every type of disease and cannot constitute a cytodiagnosis marker. Alcian Blue and hyaluronidase treatment show hyaluronate in a few percentage of Synoviocytes. Cytoenzymologic study shows that synoviocytes and monocytes are positive in all tested hydrolases: beta Glucuronidase, Acid Phosphatase, alpha Naphthyl Acetate Esterase, these activities being always higher in synoviocytes. With peroxidase, synoviocytes are always negative, so this reaction although it marks only a minority of monocytic population can be used as an extra cytologic criterion for discrimination of mononuclear cells in synovial fluid. In these four enzymes there is no significant quantitative difference at cellular level between osteoarthrosis and arthritides. Lysosomal enzymatic activity in both monocytic and synoviocytic cells confirms their heterophagic properties. However synoviocytic heterophagy seems to be a physiological process not or few affected by inflammatory events. On the opposite, monocytic heterophagy and then macrophagic transformation of monocytes appears as a major aspect of intrasynovial inflammatory reaction. If a large majority of exfoliated synoviocytes comes from A type synovial lining cells and if they belong to Mononuclear Phagocyte System, why do they so weakly, or not, participate as phagocytes to inflammatory reaction.

Topics: Acid Phosphatase; Arthritis, Reactive; Arthritis, Rheumatoid; Chondrocalcinosis; Glucuronidase; Gout; Humans; Joint Diseases; Knee Joint; Naphthol AS D Esterase; Peroxidases; Spondylitis, Ankylosing; Synovial Fluid

To obtain direct evidence for the mechanism involved in gouty inflammation, human leukocytes were incubated with synthetic monosodium urate microcrystals. To trace the phago(lyso)somal contents, colloidal carbon, ferritin, Thorotrast(R) or horseradish peroxidase was added to the incubation medium, or acid phosphatase activity was localized cytochemically. The interaction was analyzed in time sequence by electron microscopy. By 5 minutes' incubation, urate crystals and tracers had appeared in the single membrane-bounded vacuoles of leukocytes. After 30 minutes' incubation, the vacuoles containing the urate crystals and the tracers were found in more than 50% of the leukocyte population. The phago(lyso)somal membrane was occasionally discontinuous, and the tracers were found in the free cytoplasm near the membrane opening as well. After 60 minutes' or more incubation, the phago(lyso)somal changes and the cytoplasmic localization of the tracers were common, and many cells showed signs of degeneration. Urate crystals mixed in cell debris were often found to be ingested by other leukocytes. These results have been interpreted as follows. Monosodium urate crystals are avidly phagocytized. The urate crystal-containing phagosomes eventually become phagolysosomes. The phagolysosomal membrane is damaged and the contents leak out into the cytoplasm. The leakage of the hydrolases initiates the host cell injury. The urate crystals released by cell disruption are again phagocytized by other cells and the series of events are repeated.

Topics: Acid Phosphatase; Animals; Carbon; Cell Membrane; Cell Separation; Colloids; Cytoplasm; Ferritins; Gout; Horses; Humans; Hydrolases; Inclusion Bodies; Inflammation; Leukocytes; Lysosomes; Microscopy, Electron; Peroxidases; Phagocytosis; Thorium Dioxide; Time Factors; Uric Acid

Topics: Acid Phosphatase; Acute Disease; Animals; Chronic Disease; Crystallization; Dogs; Glucuronidase; Gout; Hydrogen-Ion Concentration; Knee Joint; L-Lactate Dehydrogenase; Leukocyte Count; Microscopy, Electron; Muramidase; Phagocytosis; Pressure; Synovial Fluid; Synovial Membrane; Synovitis; Time Factors; Uric Acid

Topics: Acid Phosphatase; Alkaline Phosphatase; Arthritis, Reactive; Behcet Syndrome; Buffers; Chondrocalcinosis; Gout; Histocytochemistry; Humans; Hydrarthrosis; Joint Diseases; Methods; Synovial Fluid; Ultracentrifugation

Topics: Acid Phosphatase; Chondrocalcinosis; Diphosphates; Female; Gout; Hemolysis; Humans; Inflammation; Leukocytes; Lysosomes; Male; Membranes; Phagocytosis; Sex Factors; Silicon Dioxide; Uric Acid

Topics: Acid Phosphatase; Animals; Cholesterol; Chromates; Erythrocytes; Estradiol; Female; Glucuronidase; Gout; Hemolysis; Humans; Leukocytes; Liposomes; Liver; Lysosomes; Male; Muramidase; Rabbits; Silicon Dioxide; Sucrose; Sulfatases; Testosterone; Uric Acid

Topics: Acid Phosphatase; Arginase; Arthritis, Rheumatoid; Glycoside Hydrolases; Gout; Humans; Joint Diseases; Osteoarthritis; Peptide Hydrolases; Rheumatic Diseases; Synovial Fluid; Transaminases

Topics: Acid Phosphatase; Alkaline Phosphatase; Aspartate Aminotransferases; Cytodiagnosis; Fructose-Bisphosphate Aldolase; Gout; Humans; Hydrarthrosis; Isocitrate Dehydrogenase; L-Lactate Dehydrogenase; Malate Dehydrogenase; Synovial Fluid; Uric Acid

Topics: Acid Phosphatase; Alkaline Phosphatase; Arthritis, Rheumatoid; Bursitis; Fructose-Bisphosphate Aldolase; Gout; Humans; Joint Diseases; Osteoarthritis; Phosphoric Monoester Hydrolases; Synovial Fluid; Transaminases

Topics: Acid Phosphatase; Arthritis, Rheumatoid; C-Reactive Protein; Diagnosis, Differential; Gout; Histiocytes; Humans; Joint Diseases; Synovial Fluid; Synovitis; Uric Acid; Viscosity

Topics: Acid Phosphatase; Arthritis, Infectious; Arthritis, Reactive; Arthritis, Rheumatoid; Complement Fixation Tests; Complement System Proteins; Fluorescent Antibody Technique; Glucuronidase; Gout; Hemolysis; Humans; Proteins; Synovial Fluid

Topics: Acid Phosphatase; Adolescent; Alkaline Phosphatase; Arthritis; Arthritis, Infectious; Arthritis, Rheumatoid; Chemistry Techniques, Analytical; Diagnosis; Geriatrics; Gout; Humans; Knee Injuries; Osteoarthritis; Phosphoric Monoester Hydrolases; Synovial Fluid; Synovitis; Tuberculosis; Tuberculosis, Osteoarticular