title: Extracellular matrix in multiple sclerosis lesions: Fibrillar collagens, biglycan and decorin are upregulated and associated with infiltrating immune cells.
abstract: Extracellular matrix (ECM) proteins can modify immune reactions, e.g. by sequestering or displaying growth factors and by interacting with immune and glial cells. Here we quantified by quantitative polymerase chain reaction (qPCR) expression of 50 ECM components and 34 ECM degrading enzymes in multiple sclerosis (MS) active and inactive white matter lesions. COL1A1, COL3A1, COL5A1 and COL5A2 chains were induced strongly in active lesions and even more in inactive lesions. These chains interact to form collagen types I, III and V, which are fibrillar collagens. Biglycan and decorin, which can decorate fibrillar collagens, were also induced strongly. The fibrillar collagens, biglycan and decorin were largely found between the endothelium and astrocytic glia limitans in the perivascular space where they formed a meshwork which was closely associated with infiltrating immune cells. In active lesions collagen V was also seen in the heavily infiltrated parenchyma. Fibrillar collagens I and III inhibited in vitro human monocyte production of CCL2 (MCP-1), an inflammatory chemokine involved in recruitment of immune cells. Together, ECM changes in lesions with different activities were quantified and proteins forming a perivascular fibrosis were identified. Induced fibrillar collagens may contribute to limiting enlargement of MS lesions by inhibiting the production of CCL2 by monocytes.
authors.affiliation: Institute for Clinical Neuroimmunology, Ludwig Maximilians University, Munich, Germany.
authors.forename: Hema
authors.initials: H
authors.lastname: Mohan
authors.forename: Markus
authors.initials: M
authors.lastname: Krumbholz
authors.forename: Rakhi
authors.initials: R
authors.lastname: Sharma
authors.forename: Sylvia
authors.initials: S
authors.lastname: Eisele
authors.forename: Andreas
authors.initials: A
authors.lastname: Junker
authors.forename: Michael
authors.initials: M
authors.lastname: Sixt
authors.forename: Jia
authors.initials: J
authors.lastname: Newcombe
authors.forename: Hartmut
authors.initials: H
authors.lastname: Wekerle
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
authors.forename: Edgar
authors.initials: E
authors.lastname: Meinl
mesh_terms: D058578:Biglycan / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D058575:Decorin / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005109:Extracellular Matrix / Q000473:pathology*; D024022:Fibrillar Collagens / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D009103:Multiple Sclerosis / Q000473:pathology*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D058578:Biglycan; D018925:Chemokines; D024042:Collagen Type I; D058575:Decorin; D024022:Fibrillar Collagens; D011509:Proteoglycans; D012333:RNA, Messenger
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