Abstract
The influence of lipoxygenase metabolites of arachidonic acid on proliferation and differentiation of CD34(+) cells was studied. Their effects on the CFU-GM and BFU-E progenitors were investigated by culture of CD34(+) cells in liquid or semisolid medium. Only 12-HETE (1 microM) stimulated the [(3)H]thymidine as well as BrdU incorporation and increased the number of cell divisions (PKH2 tracking). Addition of 12-HETE and 15-HETE but not of LXA(4), LXB(4), LTB(4), and LTC(4) to liquid cultures of CD34(+) cells for 3 and 8 days reduced in a time-dependent manner the number of CFU-GM and BFU-E. Both HETEs also increased the percentage of glycophorin A(+) cells while they reduced the percentage of CD34(-)/CD33(+) cells after 3 and 5 days of liquid cultures. These results show that HETE treatment stimulates proliferation and accelerates the differentiation of CD34(+) cells, mostly toward the erythroid lineage.
Copyright 2000 Academic Press.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / pharmacology
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Antigens, CD34 / analysis*
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Antigens, Differentiation / biosynthesis
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Antigens, Differentiation / drug effects
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Arachidonic Acids / metabolism
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Arachidonic Acids / pharmacology*
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Cell Count
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Cell Division / drug effects*
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Colony-Forming Units Assay
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Culture Media / pharmacology
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Dose-Response Relationship, Drug
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Erythroid Precursor Cells / cytology
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Erythroid Precursor Cells / drug effects
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Erythropoietin / pharmacology
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Hematopoietic Stem Cells / chemistry
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Hematopoietic Stem Cells / cytology
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Hematopoietic Stem Cells / drug effects*
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Humans
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Hydroxyeicosatetraenoic Acids / pharmacology
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Leukotriene B4 / pharmacology
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Lipoxins*
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Lipoxygenase / metabolism*
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Methylcellulose
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Solutions
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Thymidine / metabolism
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Time Factors
Substances
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Antigens, CD34
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Antigens, Differentiation
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Arachidonic Acids
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Culture Media
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Hydroxyeicosatetraenoic Acids
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Lipoxins
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Solutions
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lipoxin A4
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Erythropoietin
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Leukotriene B4
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12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
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15-hydroxy-5,8,11,13-eicosatetraenoic acid
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Methylcellulose
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lipoxin B4
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Lipoxygenase
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Thymidine