Research Reveals First Details of Activation-Induced Cell Death in Macrophages
By Jason Socrates Bardi
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 cellsduring
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
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.
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