A role for adenosine in sickle-cell anemia

Excessive adenosine signalling has a pathological role in sickle-cell anaemia, pointing to new therapeutic possibilities against this disease, reports a new study published online this week in Nature Medicine.

In sickle-cell anaemia, red blood cells — erythrocytes — acquire an abnormal shape. Lack of oxygen can be the initial trigger to induce this “sickling”, which eventually leads to organ damage in patients.

Yang Xia and her team found that the concentration of adenosine in the blood was elevated in mice and humans with sickle-cell disease, promoting erythrocyte sickling and rupture. These effects depended on the activation of a specific adenosine receptor, which results in the production of 2,3-diphosphoglycerate, an erythrocyte-specific metabolite that decreases the oxygen binding affinity of hemoglobin. Drugs that target this adenosine receptor may have beneficial effects in people with sickle-cell anaemia.