Brain macrophages: on the role of pericytes and perivascular cells

Pericytes are a unique cell group intimately associated with the vasculature and that appear to be present in most tissues. Their presence is generally considered to be restricted to the microvessels - arterioles, venules and particularly capillaries, where there is little or no smooth muscle. Morphologically, the pericytes exhibit a small, oval cell body with multiple processes extending for some distance along the vessel axis; these primary processes then give rise to orthogonal secondary branches which encircle the vascular wall. Through this morphology and their close association with the vasculature, the contour of the cells conforms to that of the adjacent vascular element; also, they are usually enclosed within the basal lamina of the microvasculature. While many earlier studies suggested brain pericytes as a source of macrophage activity, recent results substantiate this functional role; these recent findings include the demonstration of macrophage markers, phagocytosis and antigen presentation. Coupled with current knowledge on the entry of lymphoblasts into brain tissue and perivascular areas as potentially being the primary site of cellular interactions for production of immune responses, this places the pericytes in a position to significantly contribute to central nervous system (CNS) immune mechanisms. They may in fact be the population of brain macrophages most instrumental in the initiation of an immune response. Although these cells constitutively express several macrophage properties, they are also capable of up-regulation to display the full range of macrophage functional activity. At least, some of the pericytic macrophages are located on the surface of the basal lamina as opposed to completely within it; however, their potential transformation into microglia of the parenchyma remains an open issue. In addition to their function as macrophages, pericytes appear to serve a host of other functional roles. They are contractile and seem to serve as a smooth muscle equivalent in the capillaries performing vasoconstriction; they regulate endothelial cell properties and contribute to the stability and maintenance of blood vessels; and they appear to directly participate in coagulation through the extrinsic pathway. Also, pericytes have been suggested to be pluripotential and serve as precursors for a variety of other cell types. From these functional roles, comes their involvement in various disease processes. In association with the macrophage function, they are involved in numerous autoimmune and infectious diseases. Through their vascular role, they are involved in diabetic retinopathy and inflammation. Also, the pericytes appear to have involvement in Alzheimer's as well as other diseases. Thus, these cells are presented not only as macrophages but as a group with broad functional activities and significant potential for contributing to disease states.