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Origin, nature, and some functional considerations of intraventricular macrophages, with special reference to the
1Department of Anatomy, Faculty of Medicine, National University of Singapore, Kent Ridge.
Abstract:
Intraventricular macrophages encompass the supraependymal, free-floating, and epiplexus (Kolmer) cells; the supraependymal cells lie in close apposition to the ventricular ependyma, the epiplexus cells are closely associated with the choroid plexus epithelium, and the free-floating cells are at a variable distance from the epithelial surface. Although the three cell types are regarded as one cellular entity, the epiplexus cells preponderate. On scanning electron microscopy, the epiplexus cells display diverse morphological forms, ranging from round to bipolar to stellate, and bear a variable number of cytoplasmic processes. Transmission electron microscopy shows the presence of large numbers of lysosomes. The phagocytic nature of epiplexus cells is shown by their intense staining for nonspecific esterase and active uptake of tracers, e.g., horseradish peroxidase and rhodamine isothiocynate, administered intravenously or intraperitoneally. The mode of entry of these tracers in the cerebral ventricles is by way of transepithelial transport. In rats, the population of intraventricular macrophages increases steadily after birth until 17 days of age; thereafter, their cell population remains relatively unchanged. The early upsurge is attributed to proliferation of residential cells and/or influx of circulating monocytes/stromal macrophages through the process of "emperipolesis." The immunophenotypic features of intraventricular macrophages are consistent with other mononuclear phagocytes being immunoreactive for OX-42, OX-18, OX-6, and OX-1 and ED1 for the detection of CR3 receptors, MHC class I and II antigens, leucocyte common antigen, and macrophage antigen, respectively. The expression of these antigens is noticeably enhanced following the injection of lipopolysaccharide (LPS) into postnatal rats. Remarkably, the intraventricular macrophages are induced to express MHC class II (Ia) antigen after LPS or interferon-gamma injections. Furthermore, the expression of transferrin receptors as detected with OX-26 is also upregulated after these treatments. Epiplexus cells are also elicited to display a de novo expression of nitric oxide synthase-like immunoreactivity following intracerebral injection of LPS. They also respond vigorously to a single nonpenetrative blast. Results of our series of studies suggest that, besides their primary function as scavenger cells, the intraventricular macrophages partake in possible immunological responses and iron regulation in the ventricular system or the brain as a whole.
Insights
Intraventricular macrophages, including epiplexus cells, are phagocytic cells in the brain ventricles. Studies show they play roles in immune responses and iron regulation, with their numbers increasing post-birth.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Intraventricular macrophages, comprising supraependymal, free-floating, and epiplexus (Kolmer) cells, reside within the brain's ventricular system.
- Epiplexus cells, closely associated with the choroid plexus epithelium, are the predominant type and exhibit diverse morphologies.
Purpose of the Study:
- To investigate the phagocytic nature, developmental changes, immunophenotype, and functional roles of intraventricular macrophages.
- To explore their involvement in immune responses and iron regulation within the ventricular system.
Main Methods:
- Scanning and transmission electron microscopy to study cell morphology and lysosome presence.
- Phagocytosis assays using tracers like horseradish peroxidase and rhodamine isothiocynate.
- Immunophenotyping using markers (OX-42, OX-18, OX-6, OX-1, ED1) and stimulation with lipopolysaccharide (LPS) or interferon-gamma.
Main Results:
- Epiplexus cells are phagocytic, actively taking up tracers via transepithelial transport.
- Intraventricular macrophage populations increase significantly in early postnatal life.
- Macrophages express key immune markers (CR3, MHC I/II, leukocyte common antigen) which are upregulated by LPS, and can express nitric oxide synthase.
Conclusions:
- Intraventricular macrophages are scavenger cells with significant roles in brain immunity and iron homeostasis.
- Their development and activation patterns suggest active participation in the central nervous system's defense and regulatory mechanisms.