Effects of lipoxygenase metabolites of arachidonic acid on the growth of human blood CD34(+) progenitors.
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.
Desplat
V
V
Laboratoire d'Hématologie Expérimentale, Faculté de Médecine, 2 rue Dr. Marcland, 87025 Limoges, France. praloran@unilim.fr
Ivanovic
Z
Z
Dupuis
F
F
Faucher
J L
JL
Denizot
Y
Y
Praloran
V
V
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000494:pharmacology; D018952:Antigens, CD34 / Q000032:analysis*; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000187:drug effects; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D003470:Culture Media / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology; D007975:Leukotriene B4 / Q000494:pharmacology; D044045:Lipoxins; D008084:Lipoxygenase / Q000378:metabolism*; D008747:Methylcellulose; D012996:Solutions; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors
D018952:Antigens, CD34; D000943:Antigens, Differentiation; D001095:Arachidonic Acids; D003470:Culture Media; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D012996:Solutions; C040527:lipoxin A4; D004921:Erythropoietin; D007975:Leukotriene B4; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D008747:Methylcellulose; C042651:lipoxin B4; D008084:Lipoxygenase; D013936:Thymidine