Endothelial Cell Laminin Isoforms, Laminins 8 and 10, Play Decisive Roles in T Cell Recruitment across the Blood–Brain Barrier in Experimental Autoimmune Encephalomyelitis
| Autor: | Rupert Hallmann, Olaf Wendler, Friederike Pausch, Lydia Sorokin, Britta Engelhardt, Michael Sixt |
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| Rok vydání: | 2001 |
| Předmět: |
Encephalomyelitis
Autoimmune Experimental endothelium Endothelium T-Lymphocytes T cell experimental autoimmune encephalomyelitis Mice Inbred Strains Blood–brain barrier Basement Membrane Receptors Laminin Extracellular matrix Mice Meninges laminin Antibody Specificity Laminin Cell Adhesion medicine Animals Protein Isoforms RNA Messenger Cells Cultured Inflammation Basement membrane biology basement membranes Experimental autoimmune encephalomyelitis Brain Cell Biology medicine.disease Molecular biology Extracellular Matrix Mice Inbred C57BL Endothelial stem cell Chemotaxis Leukocyte medicine.anatomical_structure Blood-Brain Barrier biology.protein Cytokines Tetradecanoylphorbol Acetate Original Article Female |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| DOI: | 10.1083/jcb.153.5.933 |
| Popis: | An active involvement of blood–brain barrier endothelial cell basement membranes in development of inflammatory lesions in the central nervous system (CNS) has not been considered to date. Here we investigated the molecular composition and possible function of the extracellular matrix encountered by extravasating T lymphocytes during experimental autoimmune encephalomyelitis (EAE).Endothelial basement membranes contained laminin 8 (α4β1γ1) and/or 10 (α5β1γ1) and their expression was influenced by proinflammatory cytokines or angiostatic agents. T cells emigrating into the CNS during EAE encountered two biochemically distinct basement membranes, the endothelial (containing laminins 8 and 10) and the parenchymal (containing laminins 1 and 2) basement membranes. However, inflammatory cuffs occurred exclusively around endothelial basement membranes containing laminin 8, whereas in the presence of laminin 10 no infiltration was detectable. In vitro assays using encephalitogenic T cell lines revealed adhesion to laminins 8 and 10, whereas binding to laminins 1 and 2 could not be induced. Downregulation of integrin α6 on cerebral endothelium at sites of T cell infiltration, plus a high turnover of laminin 8 at these sites, suggested two possible roles for laminin 8 in the endothelial basement membrane: one at the level of the endothelial cells resulting in reduced adhesion and, thereby, increased penetrability of the monolayer; and secondly at the level of the T cells providing direct signals to the transmigrating cells. |
| Databáze: | OpenAIRE |
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