Pigment epithelium-derived factor (PEDF) has direct effects on the metabolism and proliferation of microglia and indirect effects on astrocytes
Pigment epithelium‐derived factor (PEDF), a neurotrophic agent first identified in conditioned medium from cultured human retinal pigment epithelial cells, induces neuronal differentiation with neurite outgrowth in Y‐79 retinoblastoma cells and has a neurotrophic survival effect on cerebellar granul...
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Published in | Journal of neuroscience research Vol. 49; no. 6; pp. 710 - 718 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
New York
John Wiley & Sons, Inc
15.09.1997
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Subjects | |
Online Access | Get full text |
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Summary: | Pigment epithelium‐derived factor (PEDF), a neurotrophic agent first identified in conditioned medium from cultured human retinal pigment epithelial cells, induces neuronal differentiation with neurite outgrowth in Y‐79 retinoblastoma cells and has a neurotrophic survival effect on cerebellar granule cells in culture. In the present study, we investigated the effects of human recombinant PEDF (rPEDF) on proliferation and activation of microglia and astrocytes isolated from newborn rat brain. rPEDF treatment caused microglia to round up morphologically, increased their metabolic activity (measured by both MTS conversion and acid phosphatase activity), but blocked proliferation (mitosis). This blocking effect could be demonstrated in cultures stimulated to proliferate by addition of granulocyte‐macrophage colony stimulating factor. The effect of rPEDF on microglial metabolic activity showed a dose–response relationship both in serum‐containing medium and in chemically defined medium and was blocked with anti‐PEDF antibody. rPEDF had no direct effect on the metabolic activity or proliferation of cultured astrocytes but blocked their proliferation in astrocyte‐microglia co‐cultures. Proliferation of isolated astrocytes was also blocked by conditioned medium from microglia treated with PEDF (PMCM). The effect of PMCM on astrocytes was not blocked by an antibody to transforming growth factor‐β. These results demonstrate that PEDF activates microglial metabolism while blocking proliferation and suggest that a soluble factor(s) released by rPEDF‐stimulated microglia blocks the proliferation of astrocytes. Thus, PEDF could play an important role in regulation of glial function and proliferation in the central nervous system. J. Neurosci. Res. 49:710–718, 1997. Published 1997 Wiley‐Liss, Inc.
This article is a US government work and, as such, is in the public domain in the United States of America. |
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Bibliography: | istex:47AAF60E52B4D5A7066BE91573BAA5A4CFE98B42 ark:/67375/WNG-VHNDVQFW-W ArticleID:JNR5 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/(SICI)1097-4547(19970915)49:6<710::AID-JNR5>3.0.CO;2-A |