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Immature human megakaryocytes produce nuclear-associated
acetylcholinesterase
E Lev-Lehman, V Deutsch, A Eldor and H Soreq
Department of Biological Chemistry, The Life Sciences Institute, the Hebrew
University of Jerusalem, Israel.
Acetylcholinesterase (AChE) is expressed in murine megakaryocytes (MK),
where its antisense inhibition suppresses differentiation, yet was never
detected in human MK. Here, we report that AChE is produced in normal human
bone marrow MK and in cell lines derived thereof. Reverse
transcriptase-polymerase chain reaction (RT-PCR) amplification showed two
ACHEmRNA forms in human megakaryoblastic DAMI cells. In situ hybridization
demonstrated ACHEmRNA surrounding the nucleus of small DAMI cells and the
nuclear lobes of large, polyploid cells. Differentiation induction with
phorbol ester and exposure to recombinant human thrombopoietin suppressed
both ACHEmRNA and AChE activity. The residual AChE in mature differentiated
cells acquired higher stability and detergent-sensitivity as compared with
AChE in small proliferating cells. AChE activity was primarily associated
with nuclei of both DAMI cells and small (10 microm) primary proliferating
human bone marrow MK identified with GPIIb/IIIa antibodies. This activity
was significantly reduced in medium size MK (10 to 25 microm) and was
almost undetectable in large MK (>25 microm), yet was twofold more
abundant in some large MK from idiopathic thrombocytopenia purpura (ITP)
patients with accelerated MK maturation. The loss of AChE activity at the
transition from proliferating to differentiating MK highlights
species-specific differences in its expression, suggesting a distinct role
for AChE in human MK development.
Volume 89,
Issue 10,
pp. 3644-3653,
05/15/1997
Copyright © 1997 by The American Society of Hematology
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