The Role of Adenosine Signaling in Sickle Cell Therapeutics

Data suggest a role for adenosine signaling in the pathogenesis of sickle cell disease (SOD). Signaling through the adenosine A(2A) receptor (A(2A)R) has demonstrated beneficial effects. Activation of A(2A)Rs decreases inflammation with SCD by blocking activation of invariant natural killer T cells. Decreased inflammation may reduce the severity of vasoocclusive crises. Adenosine signaling through the adenosine A(2B) receptor (A(2B)R) may be detrimental in SCD. Whether adenosine signaling predominantly occurs through A(2A)Rs or A(2B)Rs may depend on differing levels of adenosine and disease state (steady state versus crisis). There may be opportunities to develop novel therapeutic approaches targeting A(2A)Rs and/or A(2B)Rs for patients with SCD.