EPIDERMAL GROWTH-FACTOR IS A MOTILITY FACTOR FOR MICROGLIAL CELLS IN-VITRO - EVIDENCE FOR EGF RECEPTOR EXPRESSION

Epidermal growth factor (EGF) and its receptor are present in the cent ral 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 encod ing 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 electro physiologically characterized microglial cells by the use of a single- cell reverse transcription-polymerase chain reaction method. Expressio n 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 contro l; migration was about half of that induced by complement 5a (10 nM), a previously described microglial chemoattractant. Chequerboard analys is showed that EGF-induced motility was composed of both chemotaxis an d 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 patholog ical 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.