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Isolation of c-kit receptor-expressing cells from bone marrow, peripheral
blood, and fetal liver: functional properties and composite antigenic
profile
T Papayannopoulou, M Brice, VC Broudy and KM Zsebo
Department of Medicine, University of Washington, Seattle 98195.
To define the cellular targets for c-kit ligand (KL) and to study their
functional properties and composite antigenic profile, we isolated cells
expressing c-kit receptor (KR) from bone marrow (BM), peripheral blood, and
fetal liver (FL) using immunoadherence to a recently obtained antibody
(SR-1) against the human KR. Cells isolated by this approach (designated
SR-1Ad) have the morphology of blasts and represent 1% to 4% of the
original BM or FL populations. SR-1Ad cells from either source are highly
enriched in progenitors (12% to 73%) and respond to KL in distinct
patterns. In SR-1Ad cells from BM, the greatest impact of KL stimulation is
on burst-forming units-erythroid (BFU-E), whereas in SR1-Ad cells from FL,
the most significant KL effect is on a mixed erythroid/nonerythroid
progenitor (erythroid/macrophage, colony-forming unit-mix [CFU-Mix]). When
antibody SR-1 is continually present in culture, it neutralizes the effects
of added KL. Furthermore, in the absence of added KL, it greatly diminishes
the erythropoietin- and interleukin-3-dependent BFU- E growth in BM;
whereas in FL, a wider spectrum of inhibition is observed, with CFU-Mix
most severely curtailed. SR-1Ad cells coexpress other progenitor-associated
antigens in a combination reflecting the dominant presence of erythroid
progenitors (high expression of CD34, DR, CD38, and Ep-1; low expression of
CD33). Several cytoadhesion molecules, ie, alpha L/beta 2 and alpha 4/beta
1 integrins, and intercellular adhesion molecule 1 and homing cell adhesion
molecule 1, are also coexpressed. Our data provide new information on the
isolation and characterization of KR expressing cells from normal, adult,
and fetal hematopoietic tissues. On these biologically relevant target
cells, the impact of ligand-induced stimulation or antibody-mediated
ablation of KR function has been gauged.
Volume 78,
Issue 6,
pp. 1403-1412,
09/15/1991
Copyright © 1991 by The American Society of Hematology
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