The trigger to cell death determines the efficiency with which dying cellsare cleared by neighbours

Phagocytosis of apoptotic cells is required to prevent tissue injury. Profe ssional phagocytes, such as monocyte-derived macrophages, are highly effici ent scavengers of apoptotic cells but their presence cannot always be relie d on; in that case, removal of effete cells is accomplished by helpful neig hbours. This study describes differences in the efficiency with which apopt otic cells of the same type, but dying in response to different triggers, a re engulfed; this varies from engulfment that is so proficient few or no un engulfed apoptotic cells are found, to engulfment that is so delayed apopto tic cells have become secondarily necrotic at the point of engulfment. In a ll cases the efficiency of engulfment is determined at least in part by the dying cells themselves. p53- and Bax-transfected kidney epithelial (293) c ells (transiently transfected using a non-toxic method) were engulfed so pr oficiently by homotypic neighbours that cells did not show evidence of enga gement of the apoptotic programme (chromatin condensation and TUNEL positiv ity) until engulfment had taken place. Engulfment nonetheless required acti vation of at least initiator caspases, 293 cells induced to apoptose by oth er means (etoposide and staurosporine treatment) were not so efficiently in gested: unengulfed apoptotic cells were consistently revealed at all doses and time points, even when treated cells were mixed with healthy, non-treat ed 293 cells. These data make it extremely unlikely that the fraction of vi able, unaffected neighbours determines the efficiency with which engulfment proceeds. Furthermore, 293 cells treated with etoposide or staurosporine w ere differentially appealing both to homotypic neighbours and to cells in t he professional phagocyte lineage (THP-1 cells), If different apoptotic sti muli programme cells to be recognised with different efficiencies, pathways to apoptosis may be injury limiting to greater or lesser degrees.