Programmed cell death or apoptosis is the most common form of eukaryotic cell death and is found during tumor regression and embryonic development. In the process of selection and eliminiation of autoreactive B and T cells apoptosis is an important process and therefore a prerequisite for the homeostasis of the immune system. Apoptosis is characterized by changes in cellular morphology (e.g. nuclear condensation, membrane bleeding) and biochemically by rapid induction on DNA fragmentation. APO-1/Fas (CD95), a member of the TNF/NGF receptor superfamily, is a glycosylated 48 kDa surface protein containing a single transmembrane region. APO-1 is expressed on a variety of human B and T cell lines, on many different tumor cells and on various normal human tissues. Triggering of APO-1 by its ligand or by certain anti-APO-1 monoclonal antibodies results in rapid induction of programmed cell death, apoptosis, in susceptible cells. The tissue distribution of APO-1 and of the APO-1 ligand suggests that the APO-1 receptor/ligand system plays an important role in various aspects of mammalian development and especially in the homeostasis of the immune system. Expression of the APO-1 cell surface protein is enhanced by IFN-g and TNF and by activation in lymphocytes. APO-1 also occurs in a soluble form (sAPO-1) devoid of a transmembrane region. Elevated sAPO-1 levels have been reported in sera from patients with high-and low-grade malignant B- and T-cell leukemias and systemic lupus erythematosus. sAPO-1 may prevent cells from undergoing APO-1 ligand induced apoptosis. Hence, secretion of sAPO-1 may provide a mechanism for tumor cells to excape immunosurveillance and may be involved in leukemogenesis.
- References to APO-1/Fas (CD95, Fas receptor, APT 1, ALPS 1 A, TNFRSF6)