On Press:
Research Reveals First Details of Activation-Induced Cell Death in Macrophages

Programmed cell death, also called apoptosis, plays an important role in biology because it is a mechanism for getting rid of cells that are no longer needed. Apoptosis plays a key role in the immune system, where it is involved in activation-induced cell death of immune cells—during the selection of T cells in the thymus and during the development of antigen tolerance in B cells, for instance. The underlying molecular mechanisms of programmed cell death in T and B cells have been extensively studied and described in recent years.

Programmed cell death has been observed in macrophages, both in vivo and in vitro. However, until recently, scientists did not understand the process of activation-induced cell death in macrophages.

Macrophages are one of the key players in the early innate immune response, and they release inflammatory chemicals known as cytokines when they are activated. This sort of inflammation is not always a good thing, and overactive macrophages have been implicated in a number of human diseases, including arthritis and sepsis. Activation-induced cell death in macrophages may present a method of controlling inflammation and avoiding these conditions.

Now the first details of activation-induced cell death in macrophages have been described in a paper by a team of researchers at The Scripps Research Institute (TSRI) led by Research Associate Sung Ouk Kim and Associate Professor Jiahuai Han.

Kim, Han, and their colleagues provide the first detailed mechanism of macrophage activation-induced cell death. This mechanism involves a receptor known as Nur77, which is also involved in T cell death. Nur77 expression is correlated with macrophage death, and macrophages deficient in Nur77 show a significant reduction in cell death.

Significantly, this mechanism seems to work independently of the protein caspase, which is central to activation-induced cell death of T cells and B cells. This new Nur77 mechanism is the first time that an example of activation-induced cell death has been found without the involvement of caspase.

To read the article "Orphan Nuclear Receptor Nur77 Is Involved in Caspase-Independent Macrophage Cell Death" by Sung Ouk Kim, Koh Ono, Peter S. Tobias, and Jiahuai Han, see the June 2, 2003 issue of J. Exp. Med. (197, 1441), or go to: http://www.jem.org/cgi/doi/10.1084/jem.20021842.


The proposed mechanism of activation-induced macrophage cell death. Click to enlarge.