Editors' ChoiceCell Biology

From Nucleoside Recycling to Histiocytosis

Science Signaling  10 Jan 2012:
Vol. 5, Issue 206, pp. ec11
DOI: 10.1126/scisignal.2002825

Macrophages remove billions of apoptotic cells daily, releasing their nucleic acid material through lysosomal degradation, which allows the resulting nucleosides to be recycled. Hsu et al. 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.

C.-L. Hsu, W. Lin, D. Seshasayee, Y.-H. Chen, X. Ding, Z. Lin, E. Suto, Z. Huang, W. P. Lee, H. Park, M. Xu, M. Sun, L. Rangell, J. L. Lutman, S. Ulufatu, E. Stefanich, C. Chalouni, M. Sagolla, L. Diehl, P. Fielder, B. Dean, M. Balazs, F. Martin, Equilibrative nucleoside transporter 3 deficiency perturbs lysosome function and macrophage homeostasis. Science 335, 89–92 (2012). [Abstract] [Full Text]