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A cell surface receptor defined by a mAb mediates a unique type of cell death similar to oncosis
1Tumor Immunology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. czhang@mbcrr.harvard.edu
Abstract:
Cell death is mediated by distinct pathways including apoptosis and oncosis in response to various death signals. To characterize molecules involved in cell death, a panel of mAbs was raised by immunizing mice with apoptotic cells. One of these antibodies, designated anti-Porimin (for pro-oncosis receptor inducing membrane injury), was found to directly induce a unique type of cell death in Jurkat cells. Anti-Porimin defines a 110-kDa cell surface receptor on Jurkat cells. Functionally, anti-Porimin alone rapidly mediates pore formation on the plasma membrane and induces cell death without participation of complement. Both the cellular expression and functional characteristics of the Porimin antigen indicate that it is distinct from the CD95 (Fas/Apo-1) and other cell receptors known to induce apoptosis. Anti-Porimin-mediated cell death was preceded by cell aggregation, formation of plasma membrane pores, and the appearance of membrane blebs. More important, these cells show neither DNA fragmentation nor apoptotic bodies, but display lethal damage of the cell membrane. Cell death by anti-Porimin is distinct from complement-dependent cytolysis or complement-independent apoptosis but is similar to that described for oncosis, a form of cell death accompanied by the membrane damage followed by karyolysis. The induction of cell death by anti-Porimin may represent a unique cell surface receptor-mediated pathway of cell death in the human lymphoid system.
Insights
Researchers identified a novel cell surface receptor, Porimin, that triggers a unique form of cell death called oncosis. This discovery offers new insights into programmed cell death pathways distinct from apoptosis.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Cell death occurs via distinct pathways like apoptosis and oncosis.
- Characterizing molecules involved in cell death is crucial for understanding cellular processes.
Purpose of the Study:
- To identify and characterize novel molecules involved in distinct cell death pathways.
- To investigate the function of a newly identified antibody, anti-Porimin, in inducing cell death.
Main Methods:
- Immunization of mice with apoptotic cells to generate monoclonal antibodies (mAbs).
- Characterization of anti-Porimin antibody and its target antigen (Porimin) on Jurkat cells.
- Analysis of cell death morphology, membrane integrity, and DNA fragmentation.
Main Results:
- Anti-Porimin antibody identified a 110-kDa cell surface receptor, Porimin, on Jurkat cells.
- Anti-Porimin induced rapid plasma membrane pore formation and cell death without complement involvement.
- Porimin-mediated cell death exhibited characteristics of oncosis, including membrane damage and karyolysis, but lacked DNA fragmentation and apoptotic bodies.
- Porimin appears distinct from known apoptosis-inducing receptors like CD95 (Fas/Apo-1).
Conclusions:
- Anti-Porimin defines a novel cell surface receptor mediating a unique pathway of cell death.
- This pathway, termed oncosis, is characterized by membrane damage and distinct from apoptosis.
- The Porimin receptor may represent a significant target for understanding and manipulating cell death in the human lymphoid system.