Brain macrophages: questions of origin and interrelationship

Brain tissue appears to contain several distinct types of macrophages. An effort is made here to present a description of the complete cohort of macrophages and sources of phagocytic activity in this tissue. Initially, the criteria and methods used for the identification of tissue macrophages in general are considered. These include some morphological and ultrastructural features, assessment of phagocytic activity, and histochemistry for intracellular and surface components. Each of these methods or criteria has certain advantages but also associated problems and limitations; all have been applied in various instances to brain tissue. In a final analysis, the most reliable means of identification of tissue macrophages involves a combination of all of these approaches. The identification and characterization of macrophages have been rendered extremely confusing in the brain because of so many different sources of these cells, both intrinsic and blood-derived. The classes of macrophages or phagocytic cells in brain tissue are microglia, supraependymal cells, epiplexus cells, meningeal macrophages, pericytes, and direct blood-derived macrophages. The morphology, location, and functional properties of each of these classes is described. In an overall view, brain tissue is very well protected by intrinsic macrophages, and the locations and distribution of these cells are consistent with other tissues. Finally, in a consideration of origin and interrelationship, the idea is presented that the most likely source for all or most brain macrophages is monocytic blood cells. The latter cells appear to migrate into the tissue from several sites during embryogenesis and may continue to enter, at least from blood vessels, in the adult state.