ROLE OF MACROSIALIN IN ATHEROSCLEROSIS AND PHAGOCYTOSIS

Massachusetts General Hospital, Boston MA

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Abstract

Macrosialin is a glycoprotein expressed mostly in the lysosome of cells of macrophage lineage. While the physiological role of macrosialin has not been characterized, macrosialin is known to bind oxidized lipoproteins. Macrophae uptake of oxidaized lipoprotein is a key event in atherosclerosis. Macrosialin's physiological function may be related to its restricted expression in the macrophage and to changes in chemical structure in a phagocytosing macrophage. I hypothesize that macrosialin contributes significantly in atherosclerosis and in maintaining lysosomal integrity and phagocytosis in the macrophage and that these functions are not mutually exclusive. This proposal intends to assess the role of macrosialin in atherosclerosis and macrophage function. Towards this end, I have generated a mouse lacking macrosialin, which will enable us to study the role of macrosialin in macrophage function and atherosclerosis. I will generate an adenovirus system carrying AU-tagged macrosialin cDNA, which will allow the reconstitution of functions ascribed to the absence of macrosialin. Elucidating a role for macrosialin in vivo would increase our understanding of macrophage biology in an inflammatory situation and in atherosclerosis.