muramidase and Multiple-Sclerosis

Immunoglobulins IgG and sIgA actively hydrolyzing histone H1 have been detected on analyzing proteolytic activity of antibodies isolated by chromatography on Protein A-agarose from blood serum of patients with multiple sclerosis and from colostrum of healthy mothers. These antibodies hydrolyze other histones less actively and virtually failed to cleave lysozyme of chicken egg. By gel filtration at acidic pH and subsequent analysis of protease activity of chromatographic fractions, it was shown that IgG and sIgA molecules were responsible for hydrolysis of histone H1. Anti-histone H1 antibodies of IgG and sIgA classes were purified by affinity chromatography on histone H1-Sepharose from catalytically active antibody preparations. The protease activity of anti-histone H1 IgG antibodies was inhibited by serine proteinase inhibitors, whereas anti-histone H1 sIgA antibodies were insensitive to inhibitors of serine, asparagine, and cysteine proteases.

Topics: Animals; Antibodies, Catalytic; Chickens; Colostrum; Female; Histones; Humans; Immunoglobulin A, Secretory; Immunoglobulin G; Multiple Sclerosis; Muramidase; Myelin Basic Protein

Mucosal administration of copolymer 1 (Cop 1, Copaxone(R), glatiramer acetate) suppresses experimental autoimmune encephalomyelitis (EAE), and is currently tested for its efficacy in the treatment of multiple sclerosis (MS). Here we demonstrate that oral treatment with Cop 1 induces, in mice, specific Th2 cells in the central nervous system (CNS), as manifested by their isolation from brains of actively sensitized Cop 1-fed mice, as well as, by the localization of orally induced Cop 1 specific suppressor cells in the brain, after their passive transfer to the periphery. Feeding with Cop 1 results in the accumulation in the CNS of cells that secrete Th2 cytokines in response to either Cop 1 or the autoantigen myelin basic protein (MBP), even in Th1 shifting environment, which consequently would lead to therapeutic effect in the MS diseased organ.

Topics: Administration, Oral; Adoptive Transfer; Animals; Anti-Infective Agents; Antigen Presentation; Antigen-Presenting Cells; Brain; Cross Reactions; Cytokines; Encephalomyelitis, Autoimmune, Experimental; Female; Glatiramer Acetate; Immunosuppressive Agents; Interleukin-12; Interleukin-4; Mice; Mice, Inbred BALB C; Multiple Sclerosis; Muramidase; Peptides; Th2 Cells

Using the monoclonal antibody HAM-56 with the avidin-biotin method on recent or archival paraffin-embedded tissue from multiple sclerosis brains, we have been able to distinguish between acute, chronic active and inactive lesions. HAM-56 stains all macrophages, monocytes and at least some microglia; it is the only pan-macrophage marker to our knowledge that can be satisfactorily used on conventional paraffin sections. A much narrower range of mainly perivascular macrophages in acute plaques of multiple sclerosis is stained with MAC-387, anti-muramidase and anti-alpha1-anti-trypsin. The acute plaques show HAM-56-stained macrophages throughout the lesion, and these macrophages exhibit profiles of phospholipid-rich myelinic bodies, which are also usually stainable with Luxol fast blue. Active ongoing lesions show a rim of macrophages at the edge of the lesion. These macrophages show profiles of large vacuoles, thought to represent the sudanophilic esterified cholesterol formed during demyelination. Inactive cases show none of these features; the few perivascular macrophages present often contain the end product of lipid peroxidation, ceroidlipofuscin.

Topics: alpha 1-Antitrypsin; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation; Biomarkers; Brain; Histocompatibility Antigens; Humans; Immunohistochemistry; Leukocyte Common Antigens; Macrophages; Membrane Glycoproteins; Multiple Sclerosis; Muramidase; Myelin Sheath

Twenty cases of acute or early multiple sclerosis have been examined using staining, histochemical or immunocytochemical methods. They had died within 6 months after initial clinical onset (12) or commencement of an "anatomically-remote" acute relapse (8). Plaques in these acute cases showed the following characteristics: lymphocytic perivascular infiltration, plaque hypercellularity, plaque macrophage infiltration and intra-macrophage myelin debris. In most cases of clinical duration of less than 12 weeks, some macrophages showed characteristic formaldehyde-resistant markers for haematogenous macrophages (muramidase, anti-alpha 11-antitrypsin, MAC and HAM56) but, with the exception of the last, these markers subsequently declined indicating a haematogenous origin for macrophages in the early lesion. Lymphocytes were prominent in perivascular (perivenous) regions but, except in one case, were only scanty in or at the demyelinating edge of plaques. Oligodendroglial hyperplasia, indicative of remyelinating activity, was seen at the edge of plaques in one quarter of these acute cases (7 times the rate seen in chronic lesions). Astrocytic activation was not apparent in the earliest stages but was usually seen from about 6 weeks onwards. The conclusion from these observations is that the prime inflammatory process is around blood vessels with usually only scanty initial inflammatory activity in the parenchyma of the brain. Macrophages emigrating from blood vessels digest myelin either as a response to inflammatory damage to the myelin or as a response to activation signals produced in either the perivascular region or plaque.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Brain; Female; Humans; Immunohistochemistry; Macrophages; Male; Middle Aged; Multiple Sclerosis; Muramidase

Lysozyme activity was measured in cerebrospinal fluid (CSF) from 114 patients with inflammatory (bacterial and serous meningitis, polyradiculitis, encephalitis) and non-inflammatory (multiple sclerosis, CNS tumors, cerebral vascular diseases) CNS diseases. Highly elevated values were found consistently in patients with bacterial meningitis. Elevated values were found also in patients with encephalitis, polyradiculitis, multiple sclerosis and CNS tumors, but a considerable overlapping between these groups and normal controls precludes the use of CSF lysozyme measurements as a diagnostic aid in the latter disease groups. Simultaneous measurements of lysozyme, albumin and IgG in CSF and serum suggested that the mechanism for increased CSF lysozyme values in bacterial meningitis is mainly a breakdown of the blood/brain barrier, whereas the increased CSF lysozyme values in the remaining groups of patients are more likely caused by production of lysozyme by cells within the meninges (neutrophilic granulocytes, monocytes?).

Topics: Blood-Brain Barrier; Brain Neoplasms; Central Nervous System Diseases; Cerebrovascular Disorders; Encephalitis; Humans; Immunoglobulin G; Male; Meningitis; Multiple Sclerosis; Muramidase; Polyradiculopathy; Serum Albumin

Topics: Absorption; Antibody Specificity; Antigens, Viral; Cardiolipins; Cell Line; Cell Membrane Permeability; Epitopes; Erythrocytes; Fluorescent Antibody Technique; Formaldehyde; gamma-Globulins; Hemagglutination Tests; Humans; Immune Sera; Immunoglobulin M; Lipids; Lysophosphatidylcholines; Measles; Measles virus; Multiple Sclerosis; Muramidase; Papain; Periodic Acid; Phospholipases; Pronase; Solvents; Trypsin

Topics: Humans; Multiple Sclerosis; Muramidase; Prednisolone; Saccharomyces

Topics: Anti-Infective Agents, Local; Antiviral Agents; Dermatologic Agents; Humans; Multiple Sclerosis; Muramidase; Psychotherapy, Multiple