BLOOD MONOCYTES AND SPLEEN MACROPHAGES DIFFERENTIATE INTO MICROGLIA-LIKE CELLS ON MONOLAYERS OF ASTROCYTES - MORPHOLOGY

Several morphological and functional properties of microglial cells, t he resident immunoeffector cells of the central nervous system (CNS), differ from those of monocytes/macrophages in other tissues. Microglia are assumed to derive from the myelomonocytic lineage, possibly as a distinct subpopulation that diverges from a common cell line early in ontogeny, invades the CNS, proliferates, and differentiates into amebo id and then ramified microglia. We tested the hypothesis that some mor phological and functional properties of microglia are induced in myelo monocytic cells by nervous tissue, specifically astrocytes. In the pre sent in vitro studies we compared the differentiation of microglia, bl ood monocytes, and spleen macrophages on acellular substrates and on m onolayers of astrocytes and fibroblasts. On acellular substrates, micr oglial cells at first acquire an ameboid morphology; later they show a few short, unbranched processes. On monolayers of pure astrocytes, mi croglial cells at first also differentiate into ameboid cells, but aft er 5 to 7 days they start to develop processes with large lamellopodia l tips. These lengthen and branch continuously during the next 2 weeks in vitro, demarcating a round to oval territory around the small elli psoid cell body. By contrast, on monolayers of fibroblasts the microgl ial cells develop an ameboid morphology, but do not grow the typical l ong branched processes of the ramified form. Blood monocytes and splee n macrophages behave indistinguishably from microglia both on acellula r and cellular substrates, i.e., on astroglia they develop the ramifie d form, while on fibroblasts they retain the ameboid shape. When micro glia, macrophages, or monocytes are cultured on coverslips on top of a strocytic monolayers, i.e., physically separated from the astroglia, b ut exposed to the medium conditioned by astrocytes, a significant prop ortion of them also develop the ramified shape. These findings indicat e that the ramified shape of microglia is induced by astrocytes. Since this morphology can also be induced in blood monocytes and macrophage s, we take this to be further evidence for the proposition that microg lial cells are derived from the myelomonocytic lineage, and, moreover, that properties of resident macrophages are largely determined by tis sue components of their host organ. (C) 1994 Wiley-Liss, Inc.