Nolte Christiane. Kirchhoff Frank. Kettenmann Helmut [a].
Epidermal growth factor is a motility factor for microglial cells in vitro: Evidence for EGF receptor expression, Journal of Neuroscience 9(8) :1690-1698, 1997.
Abstract
Epidermal growth factor (EGF) and its receptor are present in the central nervous system
and modulate a variety of neural functions. Here we show that microglial cells, the
brain-intrinsic macrophages, express the receptor for EGF and migrate in response to
EGF. Transcripts encoding the EGF receptor could be detected in purified microglial
cultures obtained from newborn mouse cortex. More specifically, cDNA fragments
derived from EGF receptor mRNA could be amplified from 21% of electrophysiologically
characterized microglial cells by the use of a single-cell reverse transcription-polymerase
chain reaction method. Expression of the protein was confirmed on rat microglia by flow
cytometry. EGF dose-dependently stimulated chemotactic migration, as revealed with a
microchemotaxis assay. The dose-response curve peaked at 10 ng/ml EGF, reaching a
3-fold increase in migration over the unstimulated control; migration was about half of that
induced by complement 5a (10 nM), a previously described microglial chemoattractant.
Chequerboard analysis showed that EGF-induced motility was composed of both
chemotaxis and chemokinesis. In contrast to its pronounced effect on cell motility, EGF
(0.01-10 ng/ml) was not a mitotic signal for microglia, as shown by lack of
bromodeoxyuridine incorporation. Acute and chronic pathological processes within the
brain stimulate the synthesis and release of immunoregulators and growth factors
(including EGF) that play a major role in the brain's response to injury. EGF may serve as
a paracrine factor to direct microglial cells to the lesion site. Moreover, since EGF is
secreted by activated microglia themselves in vivo, it may act as an autocrine modulator of
microglial cell function.
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