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Lipoxygenase metabolites of arachidonic acid modulate hematopoiesis
DS Snyder and JF Desforges
Lipoxygenase (LPO) metabolites of arachidonic acid participate in the
activation and/or proliferation of a variety of cell types. In this study,
we examined the role of LPO metabolites in controlling myelopoiesis and
erythropoiesis in vitro. Monocyte depleted cells (MDC) prepared from human
whole blood or whole mononuclear cells from human bone marrow were cultured
in methylcellulose in the presence of various growth factors. Conditioned
media containing human colony stimulating factors (CSF) or the
tumor-promoting phorbol ester, phorbol myristate acetate (PMA), were added
to induce myelopoiesis. Semipurified human erythropoietin (EPO) was added
along with an endogenous source of burst- promoting activity (BPA) to
induce erythropoiesis. The LPO inhibitor BW755C blocked all types of colony
formation in a dose-dependent manner, with ID50 of 20 and 5 micrograms/mL
for myeloid and erythroid colonies, respectively. MDC depleted of T cells
were similarly inhibited by BW755C. Similar results were seen with two
other LPO inhibitors, 1-phenyl-3-pyrazolidone and butylated hydroxyanisole.
A fourth LPO inhibitor, nordihydroguaiaretic acid, inhibited at higher
concentrations. Indomethacin, at concentrations that inhibit
cyclooxygenase, had no significant effect, either alone or in combination
with the LPO inhibitors. These results suggest that certain LPO products
may be important mediators of both CSF- and PMA-induced myelopoiesis, and
of BPA/EPO-induced erythropoiesis.
Volume 67,
Issue 6,
pp. 1675-1679,
06/01/1986
Copyright © 1986 by The American Society of Hematology
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