Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages

Almost 50% of the cells infiltrating the central nervous system (CNS) of animals with experimental allergic encephalomyelitis (EAE) are macrophages (M psi). To investigate the role of the M psi in the pathogenesis of EAE, we eliminated M psi by means of mannosylated liposomes containing dichloromethylene diphosphonate (Cl2MDP). Cl2MDP- containing liposomes injected intravenously eliminate M psi in spleen and liver. Incorporation of mannose into the lipid layers enables the liposomes to pass the blood-brain barrier (BBB). Injections of Cl2MDP- containing mannose liposomes intravenously shortly before the appearance of clinical signs, markedly suppressed the expression of clinical signs of EAE. This suppression was accompanied by a marked reduction of infiltrated M psi in the CNS. Cl2MDP-containing liposomes without mannose incorporated had no effect. Cl2MDP-containing mannosylated liposomes had no effect on plasma corticosterone levels compared with injections of saline; thus, the suppression of expression of EAE was not corticosterone mediated. These results show that the M psi within the CNS play an important role in the pathogenesis of EAE.

[1]  D. Mason,et al.  The role of the neuroendocrine system in determining genetic susceptibility to experimental allergic encephalomyelitis in the rat. , 1990, Immunology.

[2]  N. Rooijen.  The liposome-mediated macrophage ‘suicide’ technique , 1989 .

[3]  C. H. Polman,et al.  Observer agreement in the assessment of clinical signs in experimental allergic encephalomyelitis , 1989, Journal of Neuroimmunology.

[4]  D. Mason,et al.  Spontaneous recovery of rats from experimental allergic encephalomyelitis is dependent on regulation of the immune system by endogenous adrenal corticosteroids , 1989, The Journal of experimental medicine.

[5]  C. D. DE GROOT,et al.  Discrimination between different types of neuroglial cells in rat central nervous system using combined immuno- and enzyme-histochemical methods. , 1988, Immunobiology.

[6]  H. Hopf,et al.  The significance of the inflammatory reactions for the development of clinical signs in multiple sclerosis and acute experimental autoimmune encephalomyelitis as assessed by means of the spontaneous chemiluminescence activity of peripheral blood monocytes , 1988, Journal of Neuroimmunology.

[7]  H. Hartung,et al.  The role of macrophages and eicosanoids in the pathogenesis of experimental allergic neuritis. Serial clinical, electrophysiological, biochemical and morphological observations. , 1988, Brain : a journal of neurology.

[8]  G. Gregoriadis,et al.  Mannose-mediated targeted immunoadjuvant action of liposomes. , 1988, Immunology.

[9]  Y. Eto,et al.  Liposome targeting to mouse brain: mannose as a recognition marker. , 1988, Biochemical and biophysical research communications.

[10]  H. Hartung,et al.  Suppression of experimental autoimmune neuritis by the oxygen radical scavengers superoxide dismutase and catalase , 1988, Annals of neurology.

[11]  K. Toyka,et al.  The role of macrophages in experimental autoimmune neuritis induced by a P2‐Specific T‐Cell line , 1988, Annals of neurology.

[12]  P. Stahl,et al.  The structure and function of vertebrate mannose lectin-like proteins , 1988, Journal of Cell Science.

[13]  P. Campbell,et al.  Silica decreases phagocytosis and bactericidal activity of both macrophages and neutrophils in vitro. , 1986, Immunology.

[14]  C. Polman,et al.  Immunohistological analysis of macrophages in the central nervous system of Lewis rats with acute experimental allergic encephalomyelitis , 1986, Journal of Neuroimmunology.

[15]  D. Mason,et al.  Macrophage heterogeneity in the rat as delineated by two monoclonal antibodies MRC OX-41 and MRC OX-42, the latter recognizing complement receptor type 3. , 1986, Immunology.

[16]  J. Turk,et al.  Immunocytochemical identification and quantitation of mononuclear cells in the meninges during the development of chronic relapsing experimental allergic encephalomyelitis (CREAE) in the guinea pig. , 1986, Cellular immunology.

[17]  N. Van Rooijen,et al.  The effect of elimination of macrophages on the tissue distribution of liposomes containing [3H]methotrexate. , 1984, Biochimica et biophysica acta.

[18]  I. Vermes,et al.  The β-Adrenoceptor-Blocking Drug Propranolol Prevents Secretion of Immunoreactive β-Endorphin and α-Melanocyte-Stimulating Hormone in Response to Certain Stress Stimuli* , 1984 .

[19]  R. Colvin,et al.  The immunopathology of experimental allergic encephalomyelitis. I. Quantitative analysis of inflammatory cells in situ. , 1984, Journal of immunology.

[20]  N. Gonatas,et al.  Identification and quantitation of T lymphocyte subsets found in the spinal cord of the Lewis rat during acute experimental allergic encephalomyelitis. , 1983, Journal of immunology.

[21]  L. Epstein,et al.  Attachment of myelin to coated pits on macrophages in experimental allergic encephalomyelitis , 1983, Journal of the Neurological Sciences.

[22]  C. Brosnan,et al.  Protection against experimental allergic neuritis with silica quartz dust , 1982, Journal of Neuroimmunology.

[23]  I. Vermes,et al.  Hypothalamic deafferentation in the rat appears to discriminate between the anterior lobe and intermediate lobe response to stress , 1981, Neuroscience Letters.

[24]  A. Barclay.  The localization of populations of lymphocytes defined by monoclonal antibodies in rat lymphoid tissues. , 1981, Immunology.

[25]  C. Brosnan,et al.  The effects of macrophage depletion on the clinical and pathologic expression of experimental allergic encephalomyelitis. , 1981, Journal of immunology.

[26]  C. Brosnan,et al.  Proteinase inhibitors suppress the development of experimental allergic encephalomyelitis , 1980, Nature.

[27]  W. Carney,et al.  The effect of particle size on the immunodepressive properties of silica. , 1980, Journal of immunological methods.

[28]  S. Gordon,et al.  Degradation of basic protein in myelin by neutral proteases secreted by stimulated macrophages: a possible mechanism of inflammatory demyelination. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Mark J. Miller,et al.  Evidence for receptor-mediated binding of glycoproteins, glycoconjugates, and lysosomal glycosidases by alveolar macrophages. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[30]  G. Galfré,et al.  Analysis of cell surfaces by xenogeneic myeloma-hybrid antibodies: Differentiation antigens of rat lymphocytes , 1977, Cell.

[31]  S. Levine,et al.  Proteolytic enzymes in ordinary, hyperacute, monocytic and passive transfer forms of experimental allergic encephalomyelitis , 1977, Brain Research.

[32]  M. Cuzner,et al.  Myelin composition in acute and chronic multiple sclerosis in relation to cerebral lysosomal activity , 1976, Journal of the Neurological Sciences.

[33]  E. Wheelock,et al.  Effects of intravenous silica on immune and non-immune functions of the murine host. , 1975, Journal of immunology.

[34]  P. Lampert.  DEMYELINATION AND REMYELINATION IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS: FURTHER ELECTRON MICROSCOPIC OBSERVATIONS* , 1965 .

[35]  D. Glick,et al.  FLUOROMETRIC DETERMINATION OF CORTICOSTERONE AND CORTISOL IN 0.02-0.05 MILLILITERS OF PLASMA OR SUBMILLIGRAM SAMPLES OF ADRENAL TISSUE. , 1964, Endocrinology.

[36]  N. Van Rooijen.  The liposome-mediated macrophage 'suicide' technique. , 1989, Journal of immunological methods.

[37]  H. Hartung,et al.  Non-specific mechanisms of inflammation and tissue damage in MS. , 1989, Research in immunology.

[38]  E. Döpp,et al.  The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in the rat recognized by monoclonal antibodies ED1, ED2 and ED3. , 1985, Immunology.

[39]  E. Döpp,et al.  The heterogeneity of mononuclear phagocytes in lymphoid organs: distinct macrophage subpopulations in rat recognized by monoclonal antibodies ED1, ED2 and ED3. , 1985, Advances in experimental medicine and biology.