Abstract
Homotypic or heterotypic internalization of another, either living or necrotic cell is currently in the center of research interest. The active invasion of a living cell called entosis and cannibalism of cells by rapidly proliferating cancers are prominent examples. Additionally, normal healthy tissue cells are capable of non-professional phagocytosis. This project studied the relationship between non-professional phagocytosis, individual proliferation and cell cycle progression. Three mesenchymal and two epithelial normal tissue cell lines were studied for homotypic non-professional phagocytosis. Homotypic dead cells were co-incubated with adherent growing living cell layers. Living cells were synchronized by mitotic shake-off as well as Aphidicolin-treatment and phagocytotic activity was analyzed by immunostaining. Cell cycle phases were evaluated by flow cytometry. Mesenchymal and epithelial normal tissue cells were capable of internalizing dead cells. Epithelial cells had much higher non-professional phagocytotic rates than mesenchymal cells. Cells throughout the entire cell cycle were able to phagocytose. The phagocytotic rate significantly increased with progressing cell cycle phases. Mitotic cells regularly phagocytosed dead cells, this was verified by Nocodazole and Colcemid treatment. Taken together, our findings indicate the ability of human tissue cells to phagocytose necrotic neighboring cells in confluent cell layers. The origin of the cell line influences the rate of cell-in-cell structure formation. The higher cell-in-cell structure rates during cell cycle progression might be influenced by cytoskeletal reorganization during this period or indicate an evolutionary anchorage of the process. Recycling of nutrients during cell growth might also be an explanation.
Highlights
In recent years more and more attention has been paid to non-professional cell phagocytosis [1,2,3,4,5,6,7,8]
Non-professional phagocytosis was studied in cells of epithelial and mesenchymal origin growing in an adherent cell layer (Fig 1A)
The remainder of the cells grown on a slide and coincubated with red-stained, heat-treated necrotic cells formed typical cell-in-cell structures with a crescent-shaped nucleus of the host cell and a round shape of the red cell completely engulfed by the cytoskeleton of the host cell (Fig 2A)
Summary
In recent years more and more attention has been paid to non-professional cell phagocytosis [1,2,3,4,5,6,7,8]. Non-professional phagocytosis describes the mechanism of cell phagocytosis by ordinary epithelial or mesenchymal cells [3]. This phenomenon was mostly observed in cancer and has been termed cell cannibalism [9].
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