Lipocortin 1 immunoreactivity identifies microglia in adult rat brain.

Abstract

Immunohistochemical localization of two Ca(++)-binding proteins, Lipocortin 1 (LC1) and S100-beta, demonstrates two distinct classes of primitive glia in the floor plate of rat embryos. With proper fixation (formalin-lysine-periodate-acetic acid), dendritic glia in the CNS of adult rats also apparently stain for either LC1 or S100-beta in the ratio of 1:3. In order to further distinguish and identify these two glial classes, we have examined their population density, topography, and responses to localized neuron death. Neurons of the ipsilateral thalamus undergo apoptosis following cortical ablation; the contralateral thalamus serves as control. By eight days post-lesion, the number of LC1 cells in the ipsilateral thalamus has increased > 4-fold, the increase comprising primarily activated phagocytes adjacent to degenerating neurons. The S100-beta glia in the same region are virtual- ly indistinguishable from control; but background staining (apparently representing extra-cellular S100-beta) is increased. Thus, the responses of dendritic LC1 glia resemble these previously described for microglia and are quite different from the astrocytes identified by S100-beta immunoreactivity. Both dendritic and activated forms of LC1 glia stain with the microglial marker, Griffonia simplicifolia iso-lectin B4. However, before the correspondence of LC1 glia and microglia can be confirmed, two anomalies require resolution: (1) the LC1 glia are greater in number and more evenly distributed than microglia marked with other methods; (2) the dendritic LC1 glia apparently are progeny of primitive glia that form the midline raphe of the embryonic floor plate. The participation of LC1 glia in the removal of CNS debris supports the hypothesis that LC1 plays anti-inflammatory and/or immunosuppressive roles in phagocytes.