Abstract 9723572 Willliamson and Schlegel During the developent of the lymphocytes of the immune system, some cells are created which are nonfunctional, and others which react to normal body components. These lymphocytes are removed by a process of programmed cell death called apoptosis, a series of changes which can be triggered by a wide variety of circumstances, but which finally occurs by a common pathway using machinery which is ready and waiting to be activated in virtually all cells. This pathway includes one step in which the surface of the apoptotic cell is altered, and after this surface change has occurred, the cell can be recognized as q doomed cell by its neighbors. Their response is to engulf and consume the apoptotic cell before it has a chance to die and fall apart (which can result in tissue damage). The critical step in the alteration of the apoptotic cell surface is a change in the membrane which surrounds the cell. This membrane is a two- layered structure made up of phospholipids. One of these, phosphatidylserine or PS, is normally kept in the inner layer of the membrane bilayer, facing the interior. In apoptotic cells, PS appears in the external layer of the membrane because the membrane enzyme which normally keeps it inside is turned off, and a new enzyme is activated which allows it to move to the cell surface. This project will study these events in lymphocytes which grow in culture and in which apoptosis can be triggered. The object of these studies will be to try to understand how the changes in the arrangement of PS are induced. Other studies have suggested that degradative enzymes (the ICE proteases), changes in the energy producing organelles (the mitochondria), or changes in the amount of calcium inside the cell may be necessary for apoptosis to occur. These studies will determine whether these factors must be involved to change the distribution of PS in apoptotic cells. In addition, these studies will investigat e how other kinds of cells recognize the PS on the surface of the apoptotic cells after it has appeared there. %%% This research is looking at changes that occur in the cell membrane during apoptosis, programmed cell death, and the mechanisms responsible for these changes. ***
