EXPRESSION OF LFA-1-ALPHA AND ICAM-1 IN THE DEVELOPING RAT-BRAIN - A POTENTIAL MECHANISM FOR THE RECRUITMENT OF MICROGLIAL CELL PRECURSORS

Several studies agree that microglial cells derive from monocytes that infiltrate the central nervous system during development, but the pre cise mechanism by which these cells enter into the nervous tissue is s till unknown. In this way, the aim of the present study was to analyze the expression of two cell adhesion molecules involved in the recruit ment of blood leukocytes into tissues, the lymphocyte function-associa ted antigen-1 alpha (LFA-1 alpha) and the intercellular adhesion molec ule-1 (ICAM-1) in the developing rat brain (from E16 to P18). By means of immunohistochemistry, our observations showed that LFA-1 alpha and ICAM-1 were expressed in the developing rat brain with a definite dis tribution pattern and a characteristic time course of appearance. In t he embryonic period, LFA-1 alpha immunoreactivity was displayed not on ly by intravascular blood cells but also by intraparenchymal round cel ls with a horseshoe-shaped nucleus, showing the typical morphological features of monocytes. Monocyte-like cells present in the embryonic br ain parenchyma often displayed mitotic profiles. LFA-1 alpha immunohis tochemistry also revealed the presence of some LFA-1 alpha-positive ce lls belonging to the ameboid microglial population (mostly in the whit e matter from E18). In the postnatal period, LFA-1 alpha immunoreactiv ity was displayed by some ameboid microglial cells (P0-P9) and also by some ramified microglia. LFA-1 alpha immunoreactivity observed in ram ified microglia was weaker when compared to LFA-1 alpha stained ameboi d microglia. In contrast, ICAM-1 immunolabeling during the embryonic p eriod was mainly located in endothelial cells of parenchymal brain blo od vessels (principally from day E18). Blood vessels in choroid plexus and meninges also expressed ICAM-1 during the embryonic time. In post natal animals, ICAM-1 immunoreactivity was found in relation to endoth elial cells of blood vessels, but the density of ICAM-1-positive blood vessels was lower than that during the embryonic period. The gradual regulation in the expression of LFA-1 alpha by monocyte-like cells and cells of the microglial lineage, and the expression of ICAM-1 by the brain vasculature strongly suggest that the LFA-1/ICAM-1 system may be a mechanism involved in the entry of microglial cell precursors into the developing rat brain. (C) 1997 Elsevier Science B.V.