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Joel Linden, Ph.D. and his team are focused on the study of adenosine
receptors-proteins on the surface of cells that recognize adenosine and
related compounds. Adenosine production by cells is increased when
cellular energy utilization and the breakdown of adenosine tri-phosphate
(ATP) is increased. Hence, adenosine levels are raised when a cell is
stressed, activated, or when there is not enough oxygen in the cells,
such is the case in ischemic heart disease and sickle cell disease.
Linden is interested in adenosine's affect on disease processes. He
found that the adenosine receptor is a very powerful negative regulator
of many cells of the immune system including, neutrophils, macrophages
and T cells. This is important to disease because by activating
adenosine receptors, inflammatory processes can be inhibited.
Inflammation has been recognized to play an important role in many
diseases, and this discovery opens up numerous new potential treatments
for heart failure, diabetes, Crohn's disease, and sickle cell
disease-many of which are associated with a low-grade, chronic
inflammatory responses.
Linden found that many of the anti-inflammatory effects of adenosine are
actually due to their effects on natural killer t-cells (NKT), which
regulate a variety of immune responses, including the immune response
to tumors and certain infectious agents. For example, NKT cells are
involved in ischemia reperfusion injury, which is a type of inflammation
and tissue damage that occurs when you either transplant a tissue, have
a heart attack, or in the presence of microvascular ischemic episodes
which are common in sickle cell disease. The damage caused by the immune
system response in these cases is inhibited by adenosine. Tumors evade
immune surveillance in part by generating large amouts of adenosine.
This suggests that adenosine receptor blockers can be used to enhance
the effectiveness of tumor vaccines.
"We think that activating adenosine receptors has great potential to
inhibit a wide-range of inflammatory and chronic diseases including
arthritis, heart failure, atherosclerosis, type 2 diabetes and sickle
cell anemia," said Linden. "A person suffering from sickle cell anemia
can go into sudden stress-induced crisis, which causes severe pain. Our
research shows that adenosine can be used to block these painful and
destructive disease flare-ups. This is a new approach."