Within the human body, with its complex array of highly differentiated
organs and tissues, it is estimated that more than a billion cells die each
day. Most of these deaths arise from a
natural process referred to as apoptosis – programmed cell death. Since apoptosis is integral to the
functioning of a healthy organism, its mechanism has been the focus of study
for many years.
In addition to the process of apoptosis, there also exists a
mechanism for the efficient processing and clearance of the cellular debris
that is a direct result of apoptosis.
Otherwise, the accumulation of released substances from dead cells could
function as autoantigens and elicit an undesirable immune response against
normal tissue resulting in autoimmune diseases.
In addition, chronic inflammation and developmental abnormalities could
result from the buildup up cellular debris.
It has been established that the immune response to apoptotic cells
involves the mobilization of phagocytic cells whose function is to engulf the
dead or dying cells. This process
necessarily requires the expression of immune tolerance in order to prevent an
autoimmune response.
The tumor suppressor p53
protein has long been associated with the mechanism of apoptosis. However, little has been established in
regards to the putative role of p53 in the clearance of cellular debris that
results from apoptosis.
Dr. Kyoung Wan Yoon and his colleagues from the Cutaneous
Biology Research Center, Massachusetts General Hospital and Harvard Medical
School, Charlestown, MA have focused their research efforts on the elucidation
of the role of p53 in the clearance of post apoptotic cells and the
establishment of tolerance to self-antigens.
What they have shown is the following. As a result of stress upon a cell that leads
to p53-mediated apoptosis, p53 triggers the production of a protein product
from the so-called “Death Domain1a (DD1a)” gene. DD1a functions as a ligand that is
instrumental in the binding of the apoptotic cell to the phagocytic immune cell
that will eventually engulf the dead cell.
Once this engulfment occurs it subsequently triggers the binding of an
inhibitory T cell that ensures tolerance to self-antigens; thereby, preventing
untoward reactions that could lead to a disease state.
This kind of work is extremely valuable in furthering the
understanding of the mechanism of self-tolerance. Such knowledge may prove instrumental in
determining the underlying mechanisms involved in auto-immune disease.
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