Bilyy R. Structural and fuctional changes in the surface of mammalian cells undergoing apoptosis and their role in intercellular interactions and immune response

Object of the research: changes in plasma membrane (PM) glycans during cell death. The aim of the work: to characterize structural and functional changes in the PM of mammalian cells, including glycan components during cell death, and explore the impact of these changes on the intercellular interaction, development of processes of inflammation and the formation of the immune response. Methods: cell-biology, immunological, biochemical, cytological. For the first time the mechanism of surface glycoprofile was deciphered. It was established that during apoptosis changes of plasma membrane takes place, which lead to the formation of apoptotic membrane vesicles (AMV) of two types. Some AMV membranes are formed by merging of endoplasmic reticulum with cell surface, containing oligomannose glycnas; while others - are formed from PM and containe desialylated glycans. Apoptosis is accompanied by caspase 3-dependent activation of sialidase 1. Sialidases in PM of dying cells desialylate not only the surface of dead cells but also glycans of cells in their microenvironment. Some of AMV are able to selectively accumulate nuclear components - DNA and histones, and release these neoantigenes upon destruction. Modified glycans at PM of dying cells serve as receptors for macrophage cell system, ensuring efferocytosis. Oligomanose and desialylated glycans on the surface of dying cells complements each other as ligands in phagocytosis.