RECOGNITION OF PHOSPHATIDYLSERINE ON THE SURFACE OF APOPTOTIC SPERMATOGENIC CELLS AND SUBSEQUENT PHAGOCYTOSIS BY SERTOLI CELLS OF THE RAT

In a primary co-culture of spermatogenic and Sertoli cells of the rat, many spermatogenic cells die by apoptosis and are subsequently engulf ed by Sertoli cells. me investigated the mechanism of this phagocytosi s reaction. Testicular cells from 20-day-old rats were cultured, and s permatogenic cells and Sertoli cells were separated. When the recovere d spermatogenic cells were maintained without Sertoli cells, the viabi lity of the cells decreased and they became more susceptible to phagoc ytosis by Sertoli cells. Phagocytosis was severely impaired when lipos omes containing acidic phospholipids, such as phosphatidylserine, phos phatidylinositol, and cardiolipin, were included in the reaction, wher eas those consisting of neutral phospholipids showed little effect. Su ch anionic liposomes were more efficiently engulfed by Sertoli cells t han were the other neutral liposomes. Also, the number of spermatogeni c cells that exposed phosphatidylserine to the surface increased when cells were maintained in single culture. The results indicate that upo n induction of spermatogenic cell apoptosis, phosphatidylserine and pr obably other acidic phospholipids, which are normally localized in the inner leaflet of the plasma membrane, translocate to the outer leafle t and serve as a signal for phagocytosis by Sertoli cells.