Origin of microglia and their regulation by astroglia.
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C Hao
Publications and source records attributed to C Hao.
Macrophage-like cells originate from neuroepithelium in culture: characterization and properties of the macrophage-like cells.
Cultures of astroglia from C3H/HeJ mice, which are resistant to bacterial cell wall polysaccharide (LPS), initiated from embryos of Theiler stage 14 (9 days of gestation) up to Theiler stage 25 (17 days of gestation) as well as newborn animals, when subjected to nutritional deprivation, i.e. non-feeding of cultures, form large numbers of macrophage-like cells. These cells express Mac-1, Mac-3, F4/80 and Fc antigens. The cells are negative for GFAP, positive for vimentin, express Ia antigen and take up DiL-Ac-LDL. They are positive to non-specific esterase, secrete lysozyme and are phagocytic. Their morphology and ultrastructure closely resemble those of macrophages. Cultures initiated from neuroepithelium of Theiler stage 13 (8.5 days of gestation), before vascularization, when subjected to nutritional deprivation, also produce macrophage-like cells. Using spleen colony assay and methyl cellulose cultures, we were unable to detect the presence of hemopoietic (macrophage) precursor cells in astroglia cultures. This supports the hypothesis that the macrophage-like cells are of neuroectodermal origin and probably correspond to resident microglia of the CNS. Using nutritionally deprived astroglia cultures, a procedure was developed for isolation of macrophage-like cells and production of highly enriched macrophage-like (microglia) cultures.
Animals↗
Production of colony-stimulating factor-1 (CSF-1) by mouse astroglia in vitro.
We investigated whether astroglia produce any of the known macrophage growth factors, CSF-1, GM-CSF, and IL-3, and if so, whether any of these cytokines stimulate the growth of CNS macrophages. In this work we used highly enriched cell cultures of C3H/HeJ mouse neopallium: cultures of astroglia and cultures of macrophage-like cells derived from nutritionally deprived astroglia cultures. We found that astroglia in cultures accumulate in the medium, an activity that stimulates the proliferation of macrophage-like cells. The activity has been identified as CSF-1 by using growth assays of cells dependent and nondependent on CSF-1, and by radioreceptor analysis which is highly specific for CSF-1. Northern blot analysis demonstrated the presence in astroglia of CSF-1 mRNA and the presence of CSF-1 receptor (c-fms) mRNA in macrophage-like cells but not in astroglia. The astroglia did not produce GM-CSF or IL-3. We concluded that a paracrine relationship exists between astroglia production of CSF-1 and the response of macrophage-like cells to the cytokine in culture.
Animals↗
Role of microglia in senile plaque formation.
To assess the role of microglial cells in senile plaque (SP) formation, we examined the density and distribution of microglia in the temporal neocortex of three groups of nondemented individuals, chosen to represent sequential stages of SP formation (no SP, n = 14; diffuse plaques (DP) only, n = 12; both DP and neuritic plaques (NP), n = 14) and patients with Alzheimer's disease (AD, n = 11). The mean density of microglia was significantly greater in the AD group. In nondemented individuals, the presence of NP but not DP was associated with an increased number of microglial cells. Most NP (91%) were focally associated with microglial cells. DP less commonly contained microglia, however, individuals with some NP had microglia within a greater proportion of their DP (47%) than did those with only DP (19%). These findings suggest that: (a) microglia are not involved in the formation of DP; (b) the presence of NP is associated with both an overall increase in microglia and the focal aggregation of cells around NP; (c) microglia may be locally involved in the conversion of DP into NP. This final point represents the most significant aspect of this study, providing the first quantitative evidence to support a specific role for microglia in the formation of NP from DP.
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