ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation

Laurent Yvan-Charvet, Tamara Pagler, Emmanuel L. Gautier, Serine Avagyan, Read L. Siry, Seongah Han, Carrie L. Welch, Nan Wang, Gwendalyn J. Randolph, Hans W. Snoeck, Alan R. Tall

Research output: Contribution to journalArticlepeer-review

515 Scopus citations

Abstract

Elevated leukocyte cell numbers (leukocytosis), and monocytes in particular, promote atherosclerosis; however, how they become increased is poorly understood. Mice deficient in the adenosine triphosphate-binding cassette (ABC) transporters ABCAl and ABCGl, which promote cholesterol efflux from macrophages and suppress atherosclerosis in hypercholesterolemic mice, displayed leukocytosis, a transplantable myeloproliferative disorder, and a dramatic expansion of the stem and progenitor cell population containing Lin -Sca-l+Kit+ (LSK) in the bone marrow. Transplantation of Abca1-/- Abcg1-/- bone marrow into apolipoprotein A-I transgenic mice with elevated levels of high-density lipoprotein (HDL) suppressed the LSK population, reduced leukocytosis, reversed the myeloproliferative disorder, and accelerated atherosclerosis. The findings indicate that ABCAl, ABCGl, and HDL inhibit the proliferation of hematopoietic stem and multipotential progenitor cells and connect expansion of these populations with leukocytosis and accelerated atherosclerosis.

Original languageEnglish
Pages (from-to)1689-1693
Number of pages5
JournalScience
Volume328
Issue number5986
DOIs
StatePublished - Jun 25 2010

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