Administration of recombinant human interleukin-7 to mice induces the exportation of myeloid progenitor cells from the bone marrow to peripheral sites.
The administration of recombinant human interleukin-7 (rhIL-7) to mice twice a day for 7 days does not appreciably change bone marrow (BM) cellularity, but does result in a threefold to fivefold increase in the total number of leukocytes in the spleen, an eightfold to 10-fold increase in the total number of nonparenchymal cells (NPC) obtained from the liver, and up to a 20-fold increase in the total number of peripheral white blood cells (WBC). This regimen of rhIL-7 administration also causes a profound reduction in the total number of progenitors in the BM for both single-lineage colony-forming units-culture (CFU-c) (> 90%) and multilineage CFU-granulocyte, erythroid, monocyte, megakaryocyte (CFU-GEMM) (> 99%) colonies. In contrast, mice treated with rhIL-7 exhibited increases in both CFU-c (20- to 40-fold, 20-fold, and 15- to 40-fold) and CFU-GEMM (8- to 10-fold, 30-fold, and 6- to 10-fold) cultured from the peripheral blood, spleen, and NPC, respectively. The increase in CFU in the NPC was accompanied by a fivefold increase in the number of MAC-1+ cells and a ninefold increase in the number of 8C5bright+ cells. Splenectomy of mice before the administration of rhIL-7 further increased the total number of WBC, NPC, and myeloid progenitors as compared with the rhIL-7-treated nonsplenectomized mice. Finally, selective depletion of the BM by intraperitoneal administration of 89Sr (98% reduction in BM cellularity and > 99% reduction in BM myeloid progenitors) abrogated the rhIL-7-induced increases in cellularity and myeloid progenitor number in the peripheral blood, spleen, and NPC. These results show that the changes in myelopoiesis observed after in vivo administration of rhIL-7 to mice result largely from the emigration of myeloid progenitors from the BM through the blood to the spleen, liver, and, possibly, other peripheral organs.
Grzegorzewski
K
K
Biological Carcinogenesis and Development Program, Program Resources, Inc/DynCorp, Frederick, MD.
Komschlies
K L
KL
Mori
M
M
Kaneda
K
K
Usui
N
N
Faltynek
C R
CR
Keller
J R
JR
Ruscetti
F W
FW
Wiltrout
R H
RH
D000818:Animals; D001854:Bone Marrow Cells; D002465:Cell Movement / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000502:physiology; D015851:Interleukin-7 / Q000494:pharmacology*; D007964:Leukocytosis / Q000139:chemically induced; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D013156:Splenectomy; D013326:Strontium Radioisotopes
D015851:Interleukin-7; D011994:Recombinant Proteins; D013326:Strontium Radioisotopes