This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, W. Articles by Lee, S. C. Search for Related Content PubMed PubMed Citation Articles by Liu, W. Articles by Lee, S. C.

American Journal of Pathology, Vol 145, 48-53, Copyright © 1994 by American Society for Investigative Pathology

REGULAR ARTICLES

Macrophage colony-stimulating factor mediates astrocyte-induced microglial ramification in human fetal central nervous system culture

W Liu, CF Brosnan, DW Dickson and SC Lee
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461.

Colony-stimulating factors are important mediators of microglial growth and function. Microglia, derived from ameboid precursor cells, undergo a series of morphological changes in the central nervous system to become ramified, a morphological hallmark of differentiated microglia. The cellular mechanisms and environmental factors involved in microglial ramification in the developing brain are not known. In the present study, we examined the role of macrophage colony-stimulating factor (M-CSF) in the induction of ramification of microglia in human fetal glial cultures. Human fetal microglia underwent spontaneous conversion from ameboid to ramified shape when co-cultured with human fetal astrocytes. Concurrently, high levels of M-CSF also accumulated in cultures of unstimulated human fetal astrocytes. That the M-CSF was essential in inducing microglial ramification was demonstrated by almost complete inhibition of ramification by an antibody to human M- CSF receptor, c-fms. Furthermore, profound inhibition of microglial ramification was exerted by herbimycin A, a specific inhibitor of tyrosine kinase (a component of the signal cascade of c-fms), supporting the role of M-CSF/c-fms in the induction of microglial ramification. Our results suggest a pivotal role played by astrocytes and astrocyte-produced M-CSF in the induction of microglial maturation and differentiation in the developing human brain.

This article has been cited by other articles:

				G. R. John, S. C. Lee, and C. F. Brosnan Cytokines: Powerful Regulators of Glial Cell Activation Neuroscientist, February 1, 2003; 9(1): 10 - 22. [Abstract] [PDF]

				F. R. S. Lima, A. Gervais, C. Colin, M. Izembart, V. M. Neto, and M. Mallat Regulation of Microglial Development: A Novel Role for Thyroid Hormone J. Neurosci., March 15, 2001; 21(6): 2028 - 2038. [Abstract] [Full Text] [PDF]

				C. Eder, R. Klee, and U. Heinemann Involvement of Stretch-Activated Cl- Channels in Ramification of Murine Microglia J. Neurosci., September 15, 1998; 18(18): 7127 - 7137. [Abstract] [Full Text] [PDF]