Improving Cell Death

The process of apoptosis removes infected, mutated, and aging cells from the body. Gene-directed apoptosis, or programmed cell death, occurs normally during development and in many pathological conditions. In 1989 the cell surface receptor, Fas (CD95), was identified as the antigen recognized by antibodies that initiate cell death. Normally, Fas initiates cell death by binding the Fas ligand (FasL). Understanding and manipulating the interactions between these two proteins plays a critical role

Oct 29, 2001
Ds Culp
The process of apoptosis removes infected, mutated, and aging cells from the body. Gene-directed apoptosis, or programmed cell death, occurs normally during development and in many pathological conditions. In 1989 the cell surface receptor, Fas (CD95), was identified as the antigen recognized by antibodies that initiate cell death. Normally, Fas initiates cell death by binding the Fas ligand (FasL). Understanding and manipulating the interactions between these two proteins plays a critical role in the study and treatment of cancer, autoimmune diseases, and viral infections.

Traditionally researchers have studied the interactions between Fas and FasL using soluble FasL (sFasL) or anti-Fas monoclonal antibodies (mAbs). Now Lake Placid, N.Y.-based Upstate Biotechnology Inc. offers a less expensive and more potent research tool-a bioactive, lyophilized form of FasL on membranous vesicles.

FasL, a TNF superfamily member, is a mediator of immune responses, and the Fas/FasL system plays a pivotal role in T-cell development and clonal deletion of self-reactive T cells. Binding of FasL to its receptor activates death domain proteins, which in turn activate various caspase family members.1 The caspases, which are cysteine-dependent, aspartate-specific proteases, target specific enzymes involved in cell function, leading to cell death.

Upstate Biotechnology's preparation of FasL-expressing membranous vesicles, developed from recombinant human full-length FasL, exerts a much higher cytotoxic and apoptotic activity than that of other FasL tools.2 According to Upstate Biotechnology's John Ficele, this makes membrane-bound FasL more cost-effective than other FasL reagents. Indeed, the company's membranous FasL yields approximately 25 percent more assays for half the price of sFasL. Another advantage of these vesicles is that they can attack sFasL- and anti-Fas mAb-resistant cells.2 Researchers can further enhance the cytotoxicity of membranous FasL with either Polybrene or poly-L-lysine.2

-D.S. Culp (temos@temos.net)
References
1. J. Cortese, "Death watch II: Caspases and apoptosis," The Scientist, 15[13]:24, June 25, 2001.

2. S. Jodo et al., "Bioactivities of Fas ligand-expressing retroviral particles," Journal of Immunology, 164:5062-9, 2000.
For More Information
Upstate Biotechnology Inc.
(800) 233-3991
www.upstatebiotech.com