In vitro model of microglial deramification: Ramified microglia transform into amoeboid phagocytes following addition of brain cell membranes to microglia-astrocyte cocultures
Changes in the morphology of ramified microglia are a common feature in brain pathology and culminate in the appearance of small, rounded, microglia‐derived phagocytes in the presence of neural debris. Here, we explored the effect of adding brain cell membranes on the morphology of αMβ2‐integrin (CD...
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Published in | Journal of neuroscience research Vol. 64; no. 5; pp. 508 - 522 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
New York
John Wiley & Sons, Inc
01.06.2001
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Subjects | |
Online Access | Get full text |
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Summary: | Changes in the morphology of ramified microglia are a common feature in brain pathology and culminate in the appearance of small, rounded, microglia‐derived phagocytes in the presence of neural debris. Here, we explored the effect of adding brain cell membranes on the morphology of αMβ2‐integrin (CD11b/CD18, CR3) positive microglia cultured on a confluent astrocyte substrate as an in vitro model of deramification. Addition of brain membranes led to a loss of microglial ramification, with full transformation to small, rounded, macrophages at 20–40 μg/ml. Time course studies showed a rapid response, with first effects at 1–3 hours, and full transformation at 24–48 hours. Removal of cell membranes and exchange of the culture medium led to a similarly rapid process of reramification. Comparison of cell membranes from different tissues at 20 μg/ml showed strong transforming effect for the brain, more moderate for kidney and liver, and very weak for spleen and skeletal muscle. Fluorescent labeling of brain membranes revealed uptake by almost all rounded macrophages, by a subpopulation of glial fibrillary acidic protein (GFAP)‐positive astrocytes, but not by ramified microglia. Phagocytosis of inert fluorobeads did not lead to a transformation into macrophages but their phagocytosis was inhibited by brain membranes, pointing to a saturable uptake mechanism. In summary, addition of brain cell membranes and their phagocytosis leads to a rapid and reversible loss of ramification. The differences in transforming activity from different tissues and the absence of effect from phagocytosed fluorobeads suggest, however, the need for a second stimulus following the phagocytosis of cell debris. J. Neurosci. Res. 64:508–522, 2001. © 2001 Wiley‐Liss, Inc. |
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Bibliography: | ark:/67375/WNG-S7TMC96R-2 BMBF - No. KO 9703/3 istex:38F93C5484BE8BBAA059E5372DE6F0A886685109 DFG - No. Ra486/3-1; No. Ra486/3-2 ArticleID:JNR1103 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0360-4012 1097-4547 |
DOI: | 10.1002/jnr.1103 |