Editors' ChoiceMEDICINE

Inhibiting Leukocytosis

Science Signaling  29 Jun 2010:
Vol. 3, Issue 128, pp. ec196
DOI: 10.1126/scisignal.3128ec196

Leukocytosis—an elevated white blood cell count—contributes by unknown mechanisms to the pathogenesis of atherosclerosis and associated coronary heart disease. Now, Yvan-Charvet et al. (see the Perspective by Hansson and Björkholm) show that the ATP-binding cassette transporters ABCA1 and ABCG1 are critical suppressors of atherosclerosis-associated leukocytosis. Mice deficient in both transporters in blood-producing hematopoietic cells possessed increased levels of hematopoietic stem and multipotential progenitor cells and accelerated atherosclerosis. ABCA1 and ABCG1 protect against atherosclerosis by promoting cholesterol efflux from cholesterol-laden macrophage foam cells to lipid-poor high-density lipoprotein (HDL) and apolipoprotein A-1. The leukocytosis and atherosclerosis in ABCA1- and ABCG1-deficient mice were reversed in the presence of high amounts of HDL. Thus, signaling already known to inhibit atherosclerosis by reducing cholesterol in atherosclerotic plaques also reduces atherosclerosis-associated leukocytosis.

L. Yvan-Charvet, T. Pagler, E. L. Gautier, S. Avagyan, R. L. Siry, S. Han, C. L. Welch, N. Wang, G. J. Randolph, H. W. Snoeck, A. R. Tall, ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation. Science 328, 1689–1693 (2010). [Abstract] [Full Text]

G. K. Hansson, M. Björkholm, Tackling two diseases with HDL. Science 328, 1641–1642 (2010). [Summary] [Full Text]