Recombinant human interleukin-11 synergizes with steel factor and interleukin-3 to promote directly the early stages of murine megakaryocyte development in vitro.
The authors studied the role that interleukin (IL)-11 plays during the early stages of megakaryocyte (MK) development by investigating its in vitro effects on cell subpopulations enriched for bone marrow primitive progenitor cells and early and late committed progenitor cells. Progenitor subpopulations were isolated from bone marrow of normal or 5-fluorouracil (5FU)-treated mice and separated by sorting based on the surface antigens Sca-1, c-kit, and CD34. Functional analysis of the cell subpopulations, 5FU Lin(-)Sca-1(+)c-kit(+) or normal bone marrow (NBM) Lin(-)Sca-1(+)c-kit(+)CD34(-)cells, indicated that exposure of these cells to recombinant human (rh)IL-11 in combination with steel factor (SF) stimulates the formation of colonies in methylcellulose and their proliferation in single cell-containing liquid cultures. Kinetic studies of MK progenitor generation, in response to SF and rhIL-11, demonstrated that a significant number of the progenitors produced are committed to the MK lineage. RhIL-11 also synergized with both SF and IL-3 to stimulate MK colony growth from NBM Lin(-)Sca-1(+)c-kit(+) cells (early progenitors) and NBM Lin(-)Sca-1(-)c-kit(+) cells (committed late progenitors). In the presence of IL-3, NBM, Lin(-)Sca-1(-)c-kit(+) cells responded more strongly to rhIL-11 than SF. Consistent with these results is the observation that IL-11 receptor alpha chain mRNA is present in all the progenitor cells from which the MKs are derived. This cell culture and RNA analysis suggest that murine bone marrow primitive progenitor cells and early and late progenitor cells are direct targets of rhIL-11 and that rhIL-11 has the potential to promote megakaryocyte development at several very early stages. (Blood, 2000;95:503-509) (Blood. 2000;95:503-509)
Weich
N S
NS
Department of Tissue Growth and Repair and the Department of Immunology, Genetics Institute, Cambridge, MA.
Fitzgerald
M
M
Wang
A
A
Calvetti
J
J
Yetz-Aldape
J
J
Neben
S
S
Turner
K J
KJ
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D000950:Antigens, Ly / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D004357:Drug Synergism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D053703:Interleukin-11 Receptor alpha Subunit; D007377:Interleukin-3 / Q000494:pharmacology*; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D018123:Receptors, Interleukin / Q000235:genetics; D053702:Receptors, Interleukin-11; D011994:Recombinant Proteins / Q000494:pharmacology*; D019089:Stem Cell Factor / Q000494:pharmacology*
D018952:Antigens, CD34; D000950:Antigens, Ly; C508428:IL11RA protein, human; C508429:Il11ra1 protein, mouse; C508431:Il11ra2 protein, mouse; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D007377:Interleukin-3; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit