F4/80, an adhesion GPCR which defines the mononuclear phagocyte system

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講演要旨

Metchnikoff first conceived of the phagocytic digestive cells he observed in invertebrates and subsequently in vertebrates as belonging to a family of amoeboid tissue macrophages important in defence against infection. Aschoff introduced the term Reticulo-Endothelial System (RES) to emphasize their clearance of injected particles into the living host, but this was replaced by that of The Mononuclear Phagocyte System as a more accurate nomenclature. Forty years ago, we isolated a rat monoclonal antibody(F4/80) which was directed against a mouse macrophage antigen which turned out to be an excellent glutaradehyde-stable plasma membrane marker of most tissue macrophage populations in the body, including microglia. The antibody has been widely used to identify macrophages in development and in a broad range of experimental models of disease in adult mice. The antigen was shown to be a 7 transmembrane GPCR termed EMR1, the first of a small family of leukocyte adhesion GPCR. The ligand turned out to be elusive until now, and so far the only immunological function identified is that of peripheral tolerance to foreign antigens introduced into the anterior chamber of the eye. I shall describe the tissue expression pattern and other properties consistent with its use as a defining marker of the mononuclear phagocyte system and its potential functions as part of a multimolecular protein complex on the surface of macrophages from different species.