From Nucleoside Recycling to Histiocytosis

摘要

Macrophages remove billions of apoptotic cells daily, releasing their nucleic acid material through lyso-somal degradation, which allows the resulting nucleosides to be recycled. Hsu et al. (p. 89, published online 15 December) found that the nucleoside transporter, equilibrative nucleoside transporter 3 (ENT3), was highly expressed in macrophages and showed that mice deficient in this transporter develop histiocytosis and features of lysosomal storage disease. When exposed to apoptotic cells, macrophages carrying human ENT3 mutations accumulated adenosine and increased their lysosomal pH. These changes contributed to an enhanced signaling through macrophage colony-stimulating factor (M-CSF) receptor and, ultimately, to M-CSF-driven myeloproliferative disease.