An attempt to differentiate further between microglia and fluorescent granular perithelial (FGP) cells by their capacity to incorporate exogenous protein

Abstract

It seems established that under pathological conditions, microglia and blood monocytes (invading the cerebral parenchyma) behave as histiocytic cells in the central nervous system. However, it has not been clear whether or not phagocytic cells are present in normal cerebral tissue. Recently, we found a new type of cell having an uptake capacity for exogenous substance at the bifurcations of small cerebral vessels except for capillaries. According to Imamoto et al. (1982), ameboid microglia, a kind of precursor of microglia, appear at a perinatal stage and can incorporate exogenous material. In the present paper, the developmental sequences of ameboid microglia and the unique cells laden with fluorescent granules are compared at a light and electron-microscopic level. From this study, it is clear that ameboid microglia are already present in the corpus callosum at 5 days after birth and are potent in their uptake capacity for horseradish peroxidase (HRP). However, at 2 weeks, they transform into star cells and the capacity for incorporation diminishes markedly. The finding is also supported by the quantitative analysis of transformation of ameboid microglia. At 3 months, glial cells do not take the administered HRP under the present conditions. On the other hand, fluorescent granular perithelial (FGP) cells arise from a leptomeningeal tissue (pia mater) and become situated in the perivascular spaces. They are not clearly defined at 5 days, and their uptake capacity for HRP has not yet developed. At 2 weeks, the FGP cells take definite forms with several inclusion bodies, and their uptake capacity for HRP attains a certain degree. Often, they are located at bifurcations of small blood vessels. At 3 months, the FGP cells differentiate completely in appearance, and their pinocytotic capacity reaches a high level. Consequently, the FGP cells belong to a different type of cell from that of ameboid microglia in their developmental sequences and assume a principal role of scavenging waste products in normal cerebral tissue.

Current concepts in neuroanatomical tracing

“…The data from these experiments con®rm this hypothesis, since the rhodamine signal remained restricted to ®bres and terminals, and did not diuse into the neuropil, even after long survival times. The application results in an inevitable spreading of the tracer along the perivascular spaces, where it is phagocytosed by perivascular cells (Mato et al, 1985;Streit and Graeber, 1993). This results in a free diusion of the hydrophilic dextran amine within the cytoplasm, which leads to staining of the entire cell, as can be observed in the labelled neurones of the contralateral EC.…”

Involvement of specific macrophage-lineage cells surrounding arterioles in barrier and scavenger function in brain cortex.

“…Morphologically, the barrier is attributed to the continuous tight junctions between endothelial cells. In addition to the existence of a barrier function of capillary endothelial cells, accumulating evidence suggests the involvement of a specific type of cell in the barrier and scavenger functions in brain blood vessels (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Exogenous macromolecules injected into blood vessels or cerebral ventricles accumulated in a specific type of perivascular cell.…”

Growth retardation of Mato's fluorescent granular perithelial (FGP) cells in scavenger receptor knockout (SRKO) mice

“…They function as scavenger cells in the vascular wall and in the brain (Mato and Sakamoto, 1994;Mato et al, 1996) and are derived from pial cells surrounding blood vessels at the early stage of postnatal life (Mato et al, 1985).…”

“…As was reported previously, fine cerebral blood vessels are accompanied by novel perivascular cells (Mato's FGP cells), which exhibit a high capacity for the uptake of horseradish peroxidase (Mato et al, 1980(Mato et al, , 1985(Mato et al, , 1996. Using light and electron microscopy and immunohistochemistry, we have been engaged in the study of a specific type of perivascular macrophage, known as Mato's fluorescent granular perithelial (FGP) cells (Mato and Ookawara, 1979;Mato et al, 1980Mato et al, , 1984Mato et al, , 1985Mato et al, , 1986Mato et al, , 1989Mato and Sakamoto, 1994;Ookawara et al, 1996).…”

“…Using light and electron microscopy and immunohistochemistry, we have been engaged in the study of a specific type of perivascular macrophage, known as Mato's fluorescent granular perithelial (FGP) cells (Mato and Ookawara, 1979;Mato et al, 1980Mato et al, , 1984Mato et al, , 1985Mato et al, , 1986Mato et al, , 1989Mato and Sakamoto, 1994;Ookawara et al, 1996). We recently demonstrated the localization of the scavenger receptor on the cytoplasmic membrane of these cells (Mato et al, 1996).…”