Transbilayer phospholipid movement and the clearance of apoptotic cells

Abstract

When lymphocytes (and other cells) die by apoptosis, they orchestrate their own orderly removal by macrophages, and thereby prevent the inflammation that would otherwise attend cell lysis. As part of their demise, apoptotic cells disrupt the normal asymmetric distribution of phospholipids across their plasma membranes, an asymmetry normally maintained by an aminophospholipid translocase. This disruption of asymmetry, mediated by an activity known as the scramblase, generates ligands on the cell surface that trigger phagocytosis of the dying cell before lysis can occur. This crucial alteration of the plasma membrane is not dependent on caspase-mediated proteolysis, but quite unexpectedly, it is required both on the apoptotic target cell and on the phagocyte that engulfs it. At least in the phagocyte, this rearrangement may depend on the activity of an ABC ATPase, termed ABC1 in mammals and ced-7 in C. elegans.