acid-phosphatase and Amyloidosis

Dialysis-related amyloidosis is a complication of long-term chronic kidney disease (CKD) resulting in deposition of beta(2)-microglobulin (beta(2)M) amyloid in osteoarticular tissue. Clinical manifestations include destructive arthropathy, bone cysts, and fractures. Since osteolytic lesions are prominent findings around the beta(2)M deposits, we sought evidence whether beta(2)M causes bone destruction by directly stimulating osteoclast activity and if this was mediated by local cytokine production. A dose-dependent increase in the number of tartrate-resistant alkaline phosphatase-positive multinucleated cells was found in cultured mouse marrow cells treated with beta(2)M. Osteoprotegerin was unable to block this osteoclastogenic effect of beta(2)M. Osteoblasts or stromal cells were not necessary to induce this osteoclastogenesis, as formation was induced by incubating beta(2)M with colony-forming unit granulocyte macrophages (the earliest identified precursor of osteoclasts) or the murine RAW 264.7 monocytic cell line. beta(2)M Upregulated tumor necrosis factor-alpha (TNF-alpha) and IL-1 expression in a dose-dependent manner; however, a TNF-alpha-neutralizing antibody blocked beta(2)M-induced osteoclast formation. These results show that beta(2)M stimulates osteoclastogenesis, supporting its direct role in causing bone destruction in patients with CKD.

Topics: Acid Phosphatase; Amyloidosis; Animals; Antibodies; beta 2-Microglobulin; Bone Resorption; Calcium; Cell Line; Chronic Disease; Gene Expression; Integrin beta3; Interleukin-1; Interleukin-6; Isoenzymes; Kidney Diseases; Mice; Mice, Inbred Strains; Osteoclasts; RANK Ligand; Receptors, Calcitonin; Renal Dialysis; Skull; Tartrate-Resistant Acid Phosphatase; Tumor Necrosis Factor-alpha

Amyloidosis primarily involving bone is described in a 59-year-old male pateint. Well circumscribed lytic lesions of the skeleton raised the possibility of myelomatosis. The prolonged insidious course of the disease was uncomplicated by hypercalcemia, pathological fracture, or hematologic abnormalities. The clinical course, together with histological findings and strongly positive bone scan, were the distinguishing features. The osseous manifestations without plasma cell tumor appears to be a rare occurrence in amyloidosis.

Topics: Acid Phosphatase; Amyloidosis; Bone and Bones; Bone Resorption; Humans; Male; Middle Aged; Osteolysis; Paraproteinemias; Serum Amyloid A Protein; Technetium

Vacuoles of mesenchymal cells in the papillae of bovine kidneys with amyloidosis were studied by histochemical electron microscopy for acid phosphatase as a marker for lysosomes. The vacuoles contained parallel amyloid fibrils. The vacuoles of reticular interstitial cells were found to be lysosomes. Vacuoles of macrophage-like cells of the same papillae were positive, partially positive, or negative for the enzyme activity. A suspension of papillary material was injected subcutaneously in rats in a 21-day light and electron microscopy and enzyme histochemistry study. Amyloid was demonstrated in vacuoles of macrophages throughout this period and initially also in neutrophils. In most vacuoles amyloid fibrils were randomly arranged but in others parallel arrangement was demonstrated. Amyloid was only at the inoculation sites. Intralysosomal bovine amyloid may occur in parallel fibrillar arrangement without a definite indication for amyloid production.

Topics: Acid Phosphatase; Amyloid; Amyloidosis; Animals; Cattle; Cattle Diseases; Female; Kidney; Lysosomes; Macrophages; Phagocytosis; Vacuoles

The activity of hydrolytic and redox myeloperoxidase enzymes was determined in the neutrophils and lymphocytes of the peripheral blood of patients with secondary amyloidosis and also of the animals with amyloidogenesis and amyloidosis (caseine model). During the amyloidogenesis the activity of hyocrolytic enzymes and of myeloperoxidase in the neutrophils was found to decrease; this was particularly marked at the stage of the initial amyloid deposition. Changes in the enzyme activity in the animals against the background of already developed amyloidosis coincided with such in the blood cells of patients with secondary amyloidosis. The results obtained are discussed from the aspects of resorption theory.

Topics: Acid Phosphatase; Alkaline Phosphatase; Amyloid; Amyloidosis; Animals; Chinchilla; Glycerolphosphate Dehydrogenase; Leukocytes; Lymphocytes; Mice; Mice, Inbred C57BL; Neutrophils; Peroxidase; Rabbits; Succinate Dehydrogenase

Unusual inclusions, which occurred in the reticuloendothelial cells intimately associated with fresh amyloid deposits, were analyzed by electron microscopy. The inclusions were located in the areas rich in the primary lysosome type of dense bodies and the cytoplasmic invaginations containing well-oriented amyloid fibrils. They were single-membrane-bounded, measured 0.3 to 0.8 mu in width and 0.5 to several microns in length, and showed considerable variation in the electron density of their contents. The latter consisted of two different ultrastructural elements: fibrillar profiles and a homogeneous or finely granular electron-dense substance. The fibrillar profiles were virtually identical in ulstrastructure to the amyloid fibrils and were well-oriented parallel to the long axis of the inclusion. The homogeneous or finely granular electron-dense substance appeared to be comparable to that composing the dense body matrix. The inclusions were usually acid phosphatase positive, but did not take up intravenously injected Thorotrast particles. These data led us to conclude that these inclusions were transitional forms from the usual dense bodies to the deep cytoplasmic invaginations containing well-oriented amyloid fibrils (which are accepted by most investigators as the sites of amyloid formation) and thus constitute direct evidence for the involvement of lysosomes in amyloid fibril formation.

Topics: Acid Phosphatase; Amyloid; Amyloidosis; Animals; Disease Models, Animal; Inclusion Bodies; Lysosomes; Membranes; Mice; Mononuclear Phagocyte System; Thorium Dioxide

Electron micrsocopic studies of bovine kidneys with amyloidosis showed macrophage-like cells in the interstitial amyloid that were either disseminated or in small groups. They had rather uniform protracted vacuoles filled with parallel fibrils. Similar vacuoles were also found in some reticular interstitial cells. In some samples electron-dense vacuoles and vacuoles containing fibrils were seen. Protracted lysosomal enzyme activity was seen in macrophage-like cells and reticular interstitial cells; these areas of activity showed green birefringence with Congo red. The vacuoles were thought to be lysosomes, and the parallel amyloid fibrils could be a consequence of intracellular formation or of phagocytosis.

Topics: Acid Phosphatase; Amyloidosis; Animals; Cattle; Cattle Diseases; Endothelium; Glucuronidase; Hexosaminidases; Histocytochemistry; Kidney; Kidney Diseases; Kidney Medulla; Macrophages

Experimental amyloidosis was induced in mice with repeated injections of complete Freund's adjuvant (CFA) reinforced with bacterial vaccine. BAPN administered in a mixture with CFA or on its own before the injection of CFA reduced the incidence of amyloidosis. The reduction in the incidence of amyloidosis following the administration of BAPN may be due to its inhibitory effect on the oxidative deamination of amino acids, which presumably inhibit cross-linking of amyloid fibrils or interfere with metabolic pathways which involve the formations of mucopolysaccharide formation. It is suggested that the defective formation of the mucopolysaccharide-amyloid protein complex inhibits amyloid deposition and induces the activity of beta glucuronidase observed in the present study. The reduced incidence of amyloidosis following BAPN adminsitration cannot be due to lysosomal enzyme degradation of the amyloid as the activity of cathepsin D and acid phosphatase is decreased during this process.

Topics: Acid Phosphatase; Aminopropionitrile; Amyloidosis; Animals; Cathepsins; Drug Combinations; Freund's Adjuvant; Glucuronidase; Kidney; Liver; Mice; Spleen; Subcellular Fractions

Topics: Acid Phosphatase; Amyloidosis; Glomerulonephritis; Glycerolphosphate Dehydrogenase; Humans; Lupus Erythematosus, Systemic; Lymphocytes; Nephrotic Syndrome; Succinate Dehydrogenase

Topics: Acid Phosphatase; Alkaline Phosphatase; Amyloidosis; Familial Mediterranean Fever; Glomerulonephritis; Histocytochemistry; Humans; Lupus Erythematosus, Systemic; Neutrophils; Peroxidases

Topics: Acid Phosphatase; Alkaline Phosphatase; Amyloidosis; Glomerulonephritis; Glycerolphosphate Dehydrogenase; Humans; Leukocytes; Lupus Erythematosus, Systemic; Nephrotic Syndrome; Neutrophils; Peroxidases; Purpura; Succinate Dehydrogenase

Topics: Acid Phosphatase; Amyloid; Amyloidosis; Animals; Cathepsins; Freund's Adjuvant; Glucuronidase; Kidney; Liver; Male; Mice; Mycobacterium tuberculosis; Spleen; Time Factors

Topics: Acid Phosphatase; Amyloidosis; Biopsy; Catalase; Epithelial Cells; Epithelium; Extracellular Space; Glycosaminoglycans; Histocytochemistry; Humans; Immunoglobulins; Inclusion Bodies; Microscopy, Electron; Skin; Sodium

On the basis of recent morpholgic and biochemical studies which suggested the possible involvement of reticuloendothelial (RE) cells and proteolytic enzymes in amyloidogenesis, the present study was undertaken to examine the ultrastructural interrelationship between lysosomes and amyloid fibrils at the sites of very early amyloid deposition. In the spleen, liver and kidney of the experimental mouse model, foci of amyloid deposits were closely associated with the RE cells. The lysosomal enzyme activity, as marked by cytochemical demonstration of acid glycerophosphatase activity, was localized in the primary type lysosomes (as defined by their electron microscopic appearance), in the Golgi complexes, in the small cytoplasmic vesicles and occasionally widespread in the cytoplasm. They showed an intimate relationship to the amyloid fibrils. The findings were interpreted as favoring the hypothesis that the hydrolases play a role in amyloid fibril formation. The enzyme activity was also demonstrated in the secondary type lysosomes which occasionally contained amyloid fibrils that appeared to be phagocytized.

Topics: Acid Phosphatase; Amyloid; Amyloidosis; Animals; Caseins; Cytoplasm; Disease Models, Animal; Female; Golgi Apparatus; Histocytochemistry; Kidney; Kupffer Cells; Liver; Lysosomes; Mice; Microscopy, Electron; Mononuclear Phagocyte System; Spleen

Topics: Acid Phosphatase; Amyloid; Amyloidosis; Animals; Cathepsins; Cortisone; Freund's Adjuvant; Glucuronidase; Kidney Glomerulus; Liver; Lysosomes; Macrophages; Male; Spleen; Time Factors

Topics: Acid Phosphatase; Alkaline Phosphatase; Amyloidosis; Animals; Antigens; Beta-Globulins; Caseins; gamma-Globulins; Male; Mice; Ovalbumin; Serum Albumin; Serum Albumin, Bovine

Topics: Acid Phosphatase; Adult; Alkaline Phosphatase; Amyloidosis; Biogenic Amines; Female; Glucosephosphate Dehydrogenase; Glutamate Dehydrogenase; Glycerolphosphate Dehydrogenase; Histocytochemistry; Humans; Isocitrate Dehydrogenase; L-Lactate Dehydrogenase; Malate Dehydrogenase; Male; Middle Aged; NADH, NADPH Oxidoreductases; Phosphogluconate Dehydrogenase; Phosphoric Monoester Hydrolases; Succinate Dehydrogenase; Thyroid Gland; Thyroid Neoplasms

Topics: Acid Phosphatase; Amyloid; Amyloidosis; Animals; Cathepsins; Freund's Adjuvant; Glucuronidase; Kidney; Liver; Mice; Spleen; Time Factors

Topics: Acid Phosphatase; Adenosine Triphosphatases; Aminopeptidases; Amyloidosis; Animals; Caseins; Dihydrolipoamide Dehydrogenase; Esterases; Glucose-6-Phosphatase; Glucosephosphate Dehydrogenase; Glutamate Dehydrogenase; Glycerolphosphate Dehydrogenase; Isocitrate Dehydrogenase; L-Lactate Dehydrogenase; Malate Dehydrogenase; Male; Mice; Nucleotidases; Oxidoreductases; Phosphogluconate Dehydrogenase; Phosphoric Monoester Hydrolases; Spleen; Succinate Dehydrogenase

Topics: Acid Phosphatase; Amyloidosis; Animals; Antigens; Caseins; Fibrinogen; Freund's Adjuvant; Humans; L-Lactate Dehydrogenase; Mice; Mice, Inbred Strains; Ovalbumin; Serum Albumin

Topics: Acid Phosphatase; Amyloidosis; Animals; Antigens; Caseins; Hypersensitivity; Male; Mice; Ovalbumin; Serum Albumin

Topics: Acid Phosphatase; Aging; Amyloidosis; Animals; Axons; Brain; Brain Diseases; Cerebral Cortex; Dementia; Dog Diseases; Dogs; Histocytochemistry; Humans; Macrophages; Microscopy; Nerve Degeneration; Neuroglia

Topics: Acid Phosphatase; Alkaline Phosphatase; Amyloidosis; Animals; Caseins; Leukocytes; Lymphocytes; Mice; Neutrophils

Topics: Acid Phosphatase; Amyloidosis; Animals; Caseins; Dihydrolipoamide Dehydrogenase; Female; Glucosephosphate Dehydrogenase; Histocytochemistry; Kidney; L-Lactate Dehydrogenase; Liver; Lymph Nodes; Mechlorethamine; Mice; Nitrogen Mustard Compounds; RNA; Spleen; Staining and Labeling; Succinate Dehydrogenase

Topics: Acid Phosphatase; Amyloidosis; Animals; Animals, Newborn; Caseins; Cathepsins; Glucuronidase; Kidney; Liver; Lysosomes; Mice; Spleen

Topics: Acid Phosphatase; Amyloidosis; Animals; Caseins; Dimethyl Sulfoxide; Glycoside Hydrolases; Hydro-Lyases; In Vitro Techniques; Kidney; Liver; Lysosomes; Membranes; Peptide Hydrolases; Rats; Spleen

Topics: Acid Phosphatase; Adult; Alanine Transaminase; Alkaline Phosphatase; Amyloidosis; Aspartate Aminotransferases; Creatine Kinase; Female; Fructose-Bisphosphate Aldolase; Humans; L-Lactate Dehydrogenase; Malate Dehydrogenase; Skin; Skin Diseases