Expression of LFA-1alpha 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 precise mechanism by which these cells enter into the nervous tissue is still unknown. In this way, the aim of the present study was to analyze the expression of two cell adhesion molecules involved in the recruitment of blood leukocytes into tissues, the lymphocyte function-associated antigen-1alpha (LFA-1alpha) and the intercellular adhesion molecule-1 (ICAM-1) in the developing rat brain (from E16 to P18). By means of immunohistochemistry, our observations showed that LFA-1alpha and ICAM-1 were expressed in the developing rat brain with a definite distribution pattern and a characteristic time course of appearance. In the embryonic period, LFA-1alpha immunoreactivity was displayed not only by intravascular blood cells but also by intraparenchymal round cells with a horseshoe-shaped nucleus, showing the typical morphological features of monocytes. Monocyte-like cells present in the embryonic brain parenchyma often displayed mitotic profiles. LFA-1alpha immunohistochemistry also revealed the presence of some LFA-1alpha-positive cells belonging to the ameboid microglial population (mostly in the white matter from E18). In the postnatal period, LFA-1alpha immunoreactivity was displayed by some ameboid microglial cells (P0-P9) and also by some ramified microglia. LFA-1alpha immunoreactivity observed in ramified microglia was weaker when compared to LFA-1alpha stained ameboid microglia. In contrast, ICAM-1 immunolabeling during the embryonic period was mainly located in endothelial cells of parenchymal brain blood vessels (principally from day E18). Blood vessels in choroid plexus and meninges also expressed ICAM-1 during the embryonic time. In postnatal animals, ICAM-1 immunoreactivity was found in relation to endothelial 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-1alpha 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.