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Transforming growth factor-alpha (TGF-alpha) in human bone marrow:
demonstration of TGF-alpha in erythroblasts and eosinophilic precursor
cells and of epidermal growth factor receptors in blastlike cells of
myelomonocytic origin
TM Walz, C Malm, BK Nishikawa and A Wasteson
Department of Cell Biology, Faculty of Health Sciences, University of
Linkoping, Sweden.
The expression of transforming growth factor-alpha (TGF-alpha) in human
differentiating leukemic cell lines and in circulating human eosinophils
prompted the search for an analogous function in normal human bone marrow
(BM) cells. Immunohistochemistry, using a monoclonal antibody directed to
the mature form of the TGF-alpha molecule, showed TGF-alpha on the
erythroblasts of normal donors. This novel property of erythroid cells was
found on cells at all stages of maturation, most clearly on nucleated forms
but to some extent also on erythrocytes within the BM. The presence of
membrane-bound TGF-alpha on erythroblasts was confirmed by immunomagnetic
cell sorting with polyclonal TGF-alpha antibodies; the recovered cells
consisted almost entirely of erythroblasts. Using another monoclonal
antibody directed to TGF-alpha, immunohistochemistry showed a different
pattern of positive cells including eosinophilic precursor cells, in
accordance with earlier findings in blood eosinophils. In addition, the
TGF-alpha immunoreactivity was shown in promyelocytes and neutrophilic
myelocytes. The presence of epidermal growth factor (EGF) receptor mRNA in
BM cells was demonstrated by reverse transcription polymerase chain
reaction, whereas EGF receptor-carrying cells were recognized by
immunohistochemistry, using polyclonal antibodies directed to the
cytoplasmic part of the EGF receptor. The EGF receptor-positive cell
constituted about 3% of the nucleated BM cell population. It was classified
as a blastlike cell of myelomonocytic origin by morphologic criteria and
CD68 positivity. Our results may indicate a novel function of TGF-alpha in
erythrocytic differentiation.
Volume 85,
Issue 9,
pp. 2385-2392,
05/01/1995
Copyright © 1995 by The American Society of Hematology
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