Hematopoietic stem cells in the blood after stem cell factor and interleukin-11 administration: evidence for different mechanisms of mobilization.
Peripheral blood stem cells and progenitor cells, collected during recovery from exposure to cytotoxic agents or after cytokine administration, are being increasingly used in clinical bone marrow transplantation. To determine factors important for mobilization of both primitive stem cells and progenitor cells to the blood, we studied the blood and splenic and marrow compartments of intact and splenectomized mice after administration of recombinant human interleukin-11 (rhlL-11), recombinant rat stem cell factor (rrSCF), and IL-11 + SCF. IL-11 administration increased the number of spleen colony-forming units (CFU-S) in both the spleen and blood, but did not increase blood long-term marrow-repopulating ability (LTRA) in intact or splenectomized mice. SCF administration increased the number of CFU-S in both the spleen and blood and did not increase the blood or splenic LTRA of intact mice, but did increase blood LTRA to normal marrow levels in splenectomized mice. The combination of lL-11 + SCF syngeristically enhanced mobilization of long-term marrow-repopulating cells from the marrow to the spleen of intact mice and from the marrow to the blood of splenectomized mice. These data, combined with those of prior studies showing granulocyte colony-stimulating factor mobilization of long-term marrow repopulating cells from the marrow to the blood of mice with intact spleens, suggest different cytokine-induced pathways for mobilization of primitive stem cells.
Mauch
P
P
Joint Center for Radiation Therapy, Boston, MA 02115, USA.
Lamont
C
C
Neben
T Y
TY
Quinto
C
C
Goldman
S J
SJ
Witsell
A
A
D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects*; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D004357:Drug Synergism; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology*; D053703:Interleukin-11 Receptor alpha Subunit; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D019009:Proto-Oncogene Proteins c-kit / Q000097:blood / Q000187:drug effects / Q000502:physiology; D051381:Rats; D018123:Receptors, Interleukin / Q000145:classification / Q000187:drug effects / Q000502:physiology; D053702:Receptors, Interleukin-11; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013156:Splenectomy; D019089:Stem Cell Factor / Q000494:pharmacology*; D013268:Stimulation, Chemical
C508428:IL11RA protein, human; C508429:Il11ra1 protein, mouse; C508430:Il11ra1 protein, rat; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit