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Essential Role of Phosphatidylserine Externalization in Apoptosing Cell Phagocytosis by Macrophages

1998; Elsevier BV; Volume: 246; Issue: 2 Linguagem: Inglês

10.1006/bbrc.1998.8663

1090-2104

Akiko Shiratsuchi, Sachie Osada, Susumu Kanazawa, Yoshinobu Nakanishi,

RNA Interference and Gene Delivery

In many apoptotic cells, phosphatidylserine (PS), that is normally restricted to the inner membrane layer, is externalized and subsequently recognized by phagocytes. However, it has been unclear whether PS externalization is sufficient for phagocytosis induction. In a cultured cell line undergoing Fas-mediated apoptosis, PS externalization preceded other apoptotic events. When transbilayer movement of membrane phospholipids was analyzed, a decrease of the uptake of PS and phosphatidylethanolamine and an increase of phosphatidylcholine incorporation were observed upon apoptosis induction. Apoptotic cultured cells were phagocytosed by macrophages in a manner dependent on externalized PS before plasma membrane permeability increased. Moreover, aN-ethylmaleimide treatment caused PS externalization independent of apoptosis, and such cells underwent PS-mediated phagocytosis. These results suggested that PS is externalized as a result of membrane phospholipid redistribution and externalized PS by itself induces apoptosing cell phagocytosis.