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Blood, Vol. 94 No. 7 (October 1), 1999:
pp. 2333-2342
Demonstration That Human Mast Cells Arise From a Progenitor Cell
Population That Is CD34+, c-kit+,
and Expresses Aminopeptidase N (CD13)
Arnold S. Kirshenbaum,
Julie P. Goff,
Tekli Semere,
Barbara Foster,
Linda M. Scott, and
Dean D. Metcalfe
From Laboratory of Allergic Diseases, National Institute of Allergy
and Infectious Diseases, National Institutes of Health, Bethesda, MD;
and Department of Radiation Oncology, University of Pittsburgh Medical
Center, Pittsburgh, PA.
Human mast cells are known to arise from a
CD34+/c-kit+ progenitor cell
population that also gives rise to neutrophils, eosinophils, basophils,
and monocytes. To further characterize cells within the
CD34+/c-kit+ population that yield
mast cells, this progenitor was additionally sorted for CD13, a myeloid
marker known to appear early on rodent mast cells and cultured human
mast cells, but not expressed or expressed at low levels on human
tissue mast cells; and cultured in recombinant human (rh) stem cell
factor (rhSCF), rh interleukin-3 (rhIL-3; first week only), and rhIL-6.
Initial sorts revealed that although the majority of cells in culture
arose from the CD34+/c-kit+/CD13
cell population, mast cells arose from a
CD34+/c-kit+/CD13+
progenitor cell that also gave rise to a population of monocytes. Sequential sorting confirmed that
CD34+/c-kit+/CD13+
cells in
CD34+/c-kit+/CD13
sorts gave rise to the few mast cells observed in CD13
sorted cells.
CD34+/c-kit+/CD13+
cells plated as single cells in the presence of various cytokine combinations gave rise to pure mast cell, monocyte, or mixed mast cell/monocyte progeny. Addition of either rh
granulocyte-macrophage colony-stimulating factor
(rhGM-CSF) or rhIL-5 to the
CD34+/c-kit+/CD13+
progenitor cell population cultured in rhSCF, rhIL-3, and rhIL-6 did
increase the number of total cells cultured and in the case of rhIL-5,
did increase total mast cell numbers. Neither rhGM-CSF or rhIL-5 led to
additional cell populations, ie, even with the addition of rhGM-CSF or
rhIL-5, only mast cells and monocytes grew from
CD34+/c-kit+/CD13+
cells. Thus, human mast cells and a population of monocytes arise from
precursor cells that express CD34, c-kit, and CD13; and within which, are mast cell, monocyte, and mast/monocyte (bipotential) precursors.
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