acid-phosphatase and Multiple-Sclerosis

Topics: Acid Phosphatase; Autopsy; Axons; Biopsy; Cell Nucleus; Esterases; Glucuronidase; Glycoside Hydrolases; Humans; Inclusion Bodies; Lipid Metabolism; Lysosomes; Membranes; Microscopy, Electron; Multiple Sclerosis; Myelin Sheath; Neuroglia; Peptide Hydrolases; Phagocytosis; Phosphoric Monoester Hydrolases

Accessory molecules and cytokines are involved in the immunopathogenesis of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) in rodent models, and are potential targets for immunotherapy. Evaluation of such experimental therapies requires appropriate animal models. Therefore, we analysed the expression of selected accessory molecules and cytokines in the brain of marmoset monkeys (Callithrix jacchus) with acute EAE, a newly described non-human primate model for MS. All animals experienced active disease clinically and histopathologically with strong resemblance to MS. Perivascular infiltrates of mononuclear cells showed abundant expression of CD40. CD40 was expressed on macrophages, indicating that T cell priming and macrophage effector functions may result from local CD40-CD40L interactions. CD40 ligand (CD40L) and B7-2 (CD86) were also expressed, but to a lower extent, while B7-1 (CD80) expression was limited. Both pro-inflammatory and anti-inflammatory cytokines were produced within individual lesions during active disease (IFN-alpha, IFN-gamma, TNF-alpha, IL-1alpha, IL-1beta, IL-2, IL-4, IL-10 and IL-12). This suggests that relative levels rather than sequential expression of Th1- and Th2-type cytokines determine disease activity. These findings demonstrate the value of EAE in marmoset monkeys as a model to assess the role of accessory molecules and cytokines in multiple sclerosis, and to evaluate targeted intervention.

Topics: Acid Phosphatase; Animals; Antigens, CD; B7-1 Antigen; B7-2 Antigen; Brain; Brain Chemistry; Callithrix; CD40 Antigens; Cytokines; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Female; Histocompatibility Antigens Class II; HLA-DR Antigens; Interferon-alpha; Interferon-gamma; Interleukin-1; Interleukin-10; Interleukin-12; Interleukin-2; Interleukin-4; Macrophages; Male; Membrane Glycoproteins; Multiple Sclerosis; Tumor Necrosis Factor-alpha

One of the characteristics of ongoing demyelination in multiple sclerosis (MS) is the accumulation of lipid-laden macrophages in active lesions. Little is known about the source of these macrophages in the early stages of plaque evolution as microglial-derived and haematogenous macrophages share morphological characteristics and most cell surface antigens. A key issue in understanding the pathogenesis of MS is the reliable identification of phagocytes capable of degrading myelin and presenting autoantigen to T cells at the onset of demyelination. Using a combination of histochemistry and immunocytochemistry, an average of 60% of EBM11+ phagocytes (EMBII is a pan-macrophage marker) in early active MS plaques, defined as lesions with myelin-containing phagocytes but no obvious parenchymal myelin loss around these cells, were judged to originate from microglia as they exhibited nucleoside diphosphatase activity, a microglial marker. Only 4-15% of EBM11+ phagocytes in these lesions exhibited non-specific esterase activity, an enzyme marker for monocytes and macrophages. In contrast, 30-80% of EBM11+ phagocytes in more advanced active plaques with partial or complete myelin loss in the parenchyma were non-specific esterase+. Lysosomal enzyme acid phosphatase activity was strongly exhibited by 90% of phagocytes in all active plaques and there was a significant correlation between numbers of acid phosphatase+ cells and oil red O+ foamy macrophages. The results indicate that microglia are the main population of phagocytes in the early stages of demyelination and may play an important role in the pathogenesis of MS.

Topics: Acid Phosphatase; Adult; Aged; Apyrase; Brain; Humans; Immunohistochemistry; Lipid Metabolism; Lysosomes; Macrophages; Microglia; Middle Aged; Multiple Sclerosis; Spinal Cord

The activities of acid phosphatase and N-acetyl-beta-glucosaminidase have been measured in 171 samples of cerebrospinal fluid from 104 patients suffering from multiple sclerosis. The mean level of activity of these enzymes was lower than of controls. Patients who had the first or second bouts had somewhat higher activity of these enzymes compared to controls. The lowest values of these enzymes were found in patients with severe disability. Patients with late onset of the disease had higher levels of the enzymes compared to patients with an earlier debut of the illness, whereas patients with a short history had higher values than patients with a longer duration.

Topics: Acetylglucosaminidase; Acid Phosphatase; Adolescent; Adult; Aged; beta-Galactosidase; Female; Galactosidases; Hexosaminidases; Humans; Lysosomes; Male; Mannosidases; Middle Aged; Multiple Sclerosis

In a combined histological, biochemical and histochemical study of the macroscopically normal white matter in multipe sclerosis 72% of samples were histologically abnormal. The significance of this fact in the interpretation of previous biochemical studies and in the design of future studies is discussed. The present study showed a significant elevation of the lysosomal enzyme beta-glucosaminidase in the microscopically normal white matter in MS as compared with controls. Studies on lysosomes separated from microscopically normal or mild to moderately gliosed white matter in multiple sclerosis showed an increase in lysosomal fragility. Histochemical study of the microscopically normal white matter in multiple sclerosis revealed an increase in the number of acid phosphate-containing cells as compared with normal and neurological control material. The significance of these findings is discussed and it is suggested that irrespective of the primary or secondary nature of these abnormalities, the white matter may be rendered more susceptible to the pathogenetic process in this disease.

Topics: Acetylglucosaminidase; Acid Phosphatase; Adult; Aged; Brain; Demyelinating Diseases; Female; Gliosis; Humans; Lipofuscin; Lysosomes; Male; Middle Aged; Multiple Sclerosis

Topics: 2',3'-Cyclic-Nucleotide Phosphodiesterases; Acid Phosphatase; Brain; Brain Chemistry; Carboxylic Ester Hydrolases; Glucuronidase; Humans; Leucyl Aminopeptidase; Multiple Sclerosis; Myelin Proteins; Peptide Hydrolases

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Bone Marrow; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Neutrophils

The activities of three lysosomal enzymes were measured from the lymphocytes and granulocytes of patients with multiple sclerosis and of controls. The activity of acid phosphatase was increased in the granulocytes and that of beta-glucuronidase in the lymphocytes of MS patients in remission, as compared to those in relapse. No marked increases were observed in the activity of acid proteinase. These findings suggest that a number of lysosomal enzymes in both lymphocytes and granulocytes can be activated during demyelinating processes for reasons unknown at the moment.

Topics: Acid Phosphatase; Glucuronidase; Granulocytes; Humans; Leukocytes; Lymphocytes; Lysosomes; Multiple Sclerosis; Peptide Hydrolases

Topics: Acid Phosphatase; Animals; Demyelinating Diseases; Disease Models, Animal; DNA; Encephalomyelitis, Autoimmune, Experimental; Glucosephosphate Dehydrogenase; Haplorhini; Humans; Hydrolases; L-Lactate Dehydrogenase; Mice; Multiple Sclerosis; Wallerian Degeneration

Topics: Acid Phosphatase; Brain; DNA; Female; Galactosidases; Glucosephosphate Dehydrogenase; Glucuronidase; Humans; Hydrolases; L-Lactate Dehydrogenase; Lipase; Lipids; Middle Aged; Multiple Sclerosis; Nerve Tissue Proteins; Peptide Hydrolases; Spinal Cord

Topics: Acetylcholinesterase; Acid Phosphatase; Adenosine Triphosphatases; Adult; Alkaline Phosphatase; Autopsy; Brain; Cholinesterases; Demyelinating Diseases; Esterases; Humans; Multiple Sclerosis; Neuroglia; Phosphoric Monoester Hydrolases; Pyrophosphatases; Sulfatases; Thiamine

Topics: Acid Phosphatase; Adult; Brain; Cerebellum; Corpus Callosum; Esterases; Female; Humans; Lysosomes; Male; Microscopy, Electron; Middle Aged; Multiple Sclerosis; Myelin Sheath; Nerve Degeneration; Neuroglia; Peptide Hydrolases; Phagocytosis; Pons

Topics: Acid Phosphatase; Adolescent; Adult; Alkaline Phosphatase; Humans; Leukocytes; Middle Aged; Multiple Sclerosis

Topics: Acid Phosphatase; Adolescent; Adult; Aged; Amyotrophic Lateral Sclerosis; Blood Proteins; Female; Humans; Lysosomes; Male; Middle Aged; Multiple Sclerosis; Nerve Tissue Proteins; Sulfatases

Topics: Acid Phosphatase; Brain Chemistry; Cerebrosides; Cholesterol; Demyelinating Diseases; Humans; Lysosomes; Multiple Sclerosis; Myelin Sheath; Nerve Tissue Proteins; Nucleotides; Phospholipids; Phosphoric Monoester Hydrolases; Subacute Sclerosing Panencephalitis

Topics: Acid Phosphatase; Adenosine Triphosphatases; Animals; Animals, Newborn; Brain Neoplasms; Demyelinating Diseases; Encephalomyelitis, Autoimmune, Experimental; Esterases; Fetus; Guinea Pigs; Humans; Mice; Multiple Sclerosis; Myelin Sheath; Neuroglia; Oligodendroglioma; Phosphoric Monoester Hydrolases; Rabbits

Topics: Acetylcholinesterase; Acid Phosphatase; Adenosine Triphosphatases; Adult; Aged; Alkaline Phosphatase; Brain; Cholinesterases; Enzymes; Esterases; Female; Histocytochemistry; Humans; Male; Multiple Sclerosis; Neuroglia; Pyrophosphatases; Sulfatases

Topics: Acid Phosphatase; Alkaline Phosphatase; Brain; Brain Chemistry; Cholinesterases; Diffuse Cerebral Sclerosis of Schilder; Electrophoresis; Esterases; Humans; Multiple Sclerosis; Nucleotidases; Phosphoric Monoester Hydrolases

Topics: Acid Phosphatase; Alkaline Phosphatase; Brain; Brain Neoplasms; Carbohydrates; Electrophoresis; Esterases; Histocytochemistry; Humans; L-Lactate Dehydrogenase; Multiple Sclerosis; Proteins