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Stimulation of human myelopoiesis by leukotrienes B4 and C4: interactions
with granulocyte-macrophage colony-stimulating factor
L Stenke, M Mansour, P Reizenstein and JA Lindgren
Department of Physiological Chemistry, Karolinska Institute, Stockholm,
Sweden.
The regulatory role of leukotrienes (LT) on human myelopoiesis was
investigated. Mononuclear bone marrow cells from 31 healthy donors were
cultivated in the presence of suboptimal concentrations of recombinant
granulocyte-macrophage colony-stimulating factor (GM-CSF) for 10 days in
semisolid agar. The addition of LTC4 or LTB4 to the cultures dose-
dependently stimulated myeloid stem cell proliferation. Maximal effects
were observed at 10(-8) mol/L, at which LTC4 induced a 91% +/- 23% (mean
+/- SEM; P = .004) and LTB4 a 73% +/- 22% (P = .008) increase in colony
formation. In contrast, addition of the LTB4 isomer 5(S), 12(S)- diHETE did
not affect the growth. LTD4 exerted a weak potentiating effect on
progenitor proliferation (17% +/- 7% growth stimulation at 10(-10) mol/L; P
= .034), whereas LTE4 was without consistent effect. Furthermore,
LTC4-induced stimulation of colony formation was insensitive to the LTD4
antagonist ICI 198615. The dual lipoxygenase and prostaglandin endoperoxide
synthase inhibitor CL42A potently suppressed the proliferation of myeloid
colonies, a suppression that could be reversed by parallel addition of LTB4
or LTC4. The results suggest that both LTB4 and LTC4 possess strong and
specific synergistic stimulatory effects on GM-CSF-induced human myeloid
progenitor cell growth.
Volume 81,
Issue 2,
pp. 352-356,
01/15/1993
Copyright © 1993 by The American Society of Hematology
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