Phagocytosis of apoptotic cells: Liver recognition and molecular mechanisms

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Abstract
The engulfment of cells undergoing apoptosis can be considered a specialized form of phagocytosis, playing a major role in general tissue homeostasis in physiological and pathological conditions. Although several systems of recognition on the surface of the phagocyte have been proposed to trigger or execute the apoptotic engulfment, the nature of the molecules involved and their molecular roles are still ill defined. In the present work, the molecular mechanisms of recognition of apoptotic cells by the hepatic sinusoidal wall were further investigated. The adhesion of apoptotic cells, i.e., lymphocytes isolated from human peripheral blood and a monocytic cell line U937, was studied in in vivo and in vitro experiments. Liver endothelial cells were able to recognize apoptotic lymphocytes in vivo as well as in vitro but failed, in the same conditions, to recognize apoptotic U937. A possible explanation could derive from the differences in the cell surface glycoconjugates of apoptotic lymphocytes and U937 visualized by using a panel of fluorescent lectins. By treating endothelial cells with lipopolisaccharides or interleukin ß1, that are known to increase the number of mannose‐specific receptors on the endothelial cell surface, the adhesion of apoptotic cells doubled. Non apoptotic cells, irrespective of their source and type, normally escaped removal by sinusoidal liver cells.