title: Tissue transglutaminase in marmoset experimental multiple sclerosis: discrepancy between white and grey matter.
abstract: Infiltration of leukocytes is a major pathological event in white matter lesion formation in the brain of multiple sclerosis (MS) patients. In grey matter lesions, less infiltration of these cells occur, but microglial activation is present. Thus far, the interaction of β-integrins with extracellular matrix proteins, e.g. fibronectin, is considered to be of importance for the influx of immune cells. Recent in vitro studies indicate a possible role for the enzyme tissue Transglutaminase (TG2) in mediating cell adhesion and migration. In the present study we questioned whether TG2 is present in white and grey matter lesions observed in the marmoset model for MS. To this end, immunohistochemical studies were performed. We observed that TG2, expressed by infiltrating monocytes in white matter lesions co-expressed β1-integrin and is located in close apposition to deposited fibronectin. These data suggest an important role for TG2 in the adhesion and migration of infiltrating monocytes during white matter lesion formation. Moreover, in grey matter lesions, TG2 is mainly present in microglial cells together with some β1-integrin, whereas fibronectin is absent in these lesions. These data imply an alternative role for microglial-derived TG2 in grey matter lesions, e.g. cell proliferation. Further research should clarify the functional role of TG2 in monocytes or microglial cells in MS lesion formation.
authors: VU University Medical Center, Neuroscience Campus Amsterdam, Department of Anatomy and Neurosciences, Amsterdam, The Netherlands.
authors: Nathaly
authors: N
authors: Espitia Pinzon
authors: VU University Medical Center, Neuroscience Campus Amsterdam, Department of Anatomy and Neurosciences, Amsterdam, The Netherlands.
authors: Esther
authors: E
authors: Stroo
authors: Biomedical Primate Research Center, Department of Immunobiology, Rijswijk, The Netherlands; University Groningen, University Medical Center, Department of Neuroscience, Groningen, The Netherlands.
authors: Bert A
authors: BA
authors: 't Hart
authors: VU University Medical Center, Neuroscience Campus Amsterdam, Department of Anatomy and Neurosciences, Amsterdam, The Netherlands.
authors: John G J M
authors: JG
authors: Bol
authors: VU University Medical Center, Neuroscience Campus Amsterdam, Department of Anatomy and Neurosciences, Amsterdam, The Netherlands.
authors: Benjamin
authors: B
authors: Drukarch
authors: Center for Brain Research, Department of Neuroimmunology, Vienna, Austria.
authors: Jan
authors: J
authors: Bauer
authors: VU University Medical Center, Neuroscience Campus Amsterdam, Department of Anatomy and Neurosciences, Amsterdam, The Netherlands.
authors: Anne-Marie
authors: AM
authors: van Dam
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002144:Callithrix; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology / Q000473:pathology; D005353:Fibronectins / Q000276:immunology / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D066128:Gray Matter / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000276:immunology / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D017628:Microglia / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D009103:Multiple Sclerosis / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D009836:Oligodendroglia; D009928:Organ Specificity; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D066127:White Matter / Q000201:enzymology / Q000276:immunology / Q000473:pathology
chemical_list: D005353:Fibronectins; D019012:Integrin beta1; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins