Disparate effects of interleukin 11 and thrombopoietin on megakaryocytopoiesis in vitro.
The effects of interleukin-11 (IL-11) and thrombopoietin (TPO) on murine megakaryocytopoiesis were studied using a serum-free culture system. Acting alone, both IL-11 and TPO increased the number of acetylcholinesterase (AchE)(+)cells (megakaryocytes), the latter being more potent than the former. TPO, but not IL-11, increased the mean AchE activity per megakaryocyte (AchE activity/megakaryocyte). TPO increased both the number of megakaryocytes with high ploidy, and of those with low ploidy. In contrast, IL-11 increased only the number of megakaryocytes with high ploidy. The effect of TPO on megakaryocyte ploidy was stronger than that of IL-11. Both IL-11 and TPO increased the proportion of large megakaryocytes, but the latter was more potent than the former. While the stimulatory effects of IL-11 and TPO on the number of megakaryocytes were enhanced by IL-3 or stem cell factor (SCF), synergism of IL-11 or TPO with IL-3 or SCF in stimulating AchE activity/megakaryocyte was inconsistent. IL-11 and TPO stimulated the formation of colony-forming units of megakaryocyte in the presence of IL-3, but not alone, with similar maximum colony numbers for both cytokines. Our findings thus demonstrate that IL-11 principally stimulates megakaryocyte maturation rather than the proliferation of megakaryocytes, whereas TPO stimulates both.
Taguchi
K
K
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co. Ltd., Tsukuba-shi, Ibaraki, Japan. taguchik@yamanouchi.co.jp
Saitoh
M
M
Arai
Y
Y
Momose
K
K
Ogawa
Y
Y
Yasuda
S
S
Miyata
K
K
D000110:Acetylcholinesterase / Q000096:biosynthesis; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D017370:Interleukin-11 / Q000494:pharmacology* / Q000502:physiology*; D007377:Interleukin-3 / Q000096:biosynthesis; D008533:Megakaryocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011003:Ploidies; D011994:Recombinant Proteins / Q000378:metabolism; D019089:Stem Cell Factor / Q000096:biosynthesis; D013926:Thrombopoietin / Q000494:pharmacology* / Q000502:physiology*
D016895:Culture Media, Serum-Free; D017370:Interleukin-11; D007377:Interleukin-3; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D004247:DNA; D013926:Thrombopoietin; D000110:Acetylcholinesterase