[Apoptosis: death is part of life]

Kerr, Wyllie, and Currie who coined the term apoptosis (falling leaves in Greek) meant, among other features, to remark on the de-adhesiveness of apoptotic cells from their natural surroundings, following programmed cell death. Anoikis ("homeless" in Greek) is chronologically an inverse process: de-adhesiveness of viable cells from their surroundings inducing programmed cell death. Integrins are essential adhesive molecules in this process but additional factors probably play a role. Beyond the physiological importance, understanding these patterns will be relevant to maintain the vitality of cells used for cell therapy. Abnormal apoptosis and clearance of apoptotic cells is a fundamental factor in the pathogenesis of numerous diseases including cancer, neuro-degenerative and ischemic diseases, AIDS and autoimmunity. In systemic lupus erythematosus (SLE) the antigen responsible for most anti-DNA antibodies, exclusively generated in this disease, are derived from nucleosomes. As nucleosomes are mainly generated during programmed cell death, excess of apoptotic material and altered clearance may induce autoreactive immune responses. On the other side of the spectrum, failure to die, as exemplified in MRL/1pr mice and human lymphoproliferative disorder, may allow persistence of autoreactive cells and prevent the resolution of inflammation. When combined, we may conclude that dying properly is essential for living properly.