"Distinct Modes of Macrophage Recognition for Apoptotic and Necrotic Cells Are Not Specified Exclusively by Phosphatidyleserine Exposure."

While examining cell death is a vital part of the morphological shaping of tissues in development, this project focuses on the properties unique to the dying cells that determine the mode and outcome of phagocytic clearance of the dead cells from tissue.

Cell Death is critical in normal organismal development and homeostasis, particularly for shaping and maintaining appropriate cellular networks. We have addressed previously the fundamental question of whether a common cell-autonomous effector mechanism pertains in distinct cases of cell death. That work has led to the identification of a thematically conserved, ordered pathway for cellular destruction.

The ability of a dying cell to trigger phagocytosis without eliciting an inflammatory response likely is the overriding biological purpose of the physiological cell death process. The fundamental question in this context is how recognition without inflammatory response is assured. We have developed a novel In Vitro system with which to study this issue. We will dissect events that lead to appropriate recognition and clearance by phagocytic cells. Our quantitative methodology, which relies on clonal populations of established cell lines, offers significant scientific and technical advantages for this work, as well as eliminating the need for whole animal studies or the use of animals as a source of experimental cell populations.

As understanding of the regulation, mechanism, and outcome of the physiological cell death process will offer insights to normal cell and tissue development, and may provide new views of aging and treatments for pathological conditions, including autoimmune diseases, neurological degeneration, and cancers.