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Differentiation-associated expression of prostaglandin H and thromboxane A
synthases in monocytoid leukemia cell lines
SK Sanduja, K Mehta, XM Xu, SM Hsu, R Sanduja and KK Wu
Department of Internal Medicine, University of Texas Medical School,
Houston 77030.
To elucidate the differentiation-associated expression of enzymes
catalyzing arachidonic acid metabolism, we measured arachidonate
metabolites by reverse-phase high pressure liquid chromatography in
monocytoid leukemia (ML-1, THP-1, and U937) and myeloid leukemia (KG-1)
cell lines. Undifferentiated ML-1 or THP-1 cells produced trace amounts of
eicosanoids via the cyclooxygenase (COX) and lipoxygenase (LOX) pathways.
Upon differentiation induced by phorbol ester (phorbol 12- myristate
13-acetate [PMA]), metabolites via the COX pathway were increased by
100-fold in ML-1 and THP-1 cells, while the LOX products remained barely
detectable. All the COX metabolites were elevated, but thromboxane A2
(TXA2) formation was threefold higher in ML-1 cells than in THP-1 cells.
Similar time-related increases in COX metabolites were observed in THP-1
cells induced to differentiate with retinoic acid. Undifferentiated U937
cells were capable of generating a much higher quantity of COX products
than ML-1 or THP-1 cells, but, upon PMA- induced differentiation, COX
products were increased by only two-fold to threefold over the
undifferentiated cells and the total COX products in differentiated U937
cells were only one-seventh of those produced by differentiated ML-1 or
THP-1 cells. KG-1 cells had an entirely different metabolic profile. They
produced a large quantity of a metabolite coeluted with prostaglandin D2,
and PMA had no effect on inducing changes in arachidonic acid (AA)
metabolism. Increased COX metabolite formation in differentiated THP-1 and
ML-1 cells was due to an enhanced level of prostaglandin H synthase enzyme
mass, as measured by Western blot analysis. The TXA synthase activity was
also increased by approximately 100-fold in PMA-induced ML-1 cells and
10-fold in THP- 1 cells. These findings indicate that increased expression
of prostaglandin H and TXA synthase enzymes is a feature of differentiated
monocytoid leukemia cell lines.
Volume 78,
Issue 12,
pp. 3178-3185,
12/15/1991
Copyright © 1991 by The American Society of Hematology
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