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Administration of recombinant human interleukin-7 to mice induces the
exportation of myeloid progenitor cells from the bone marrow to peripheral
sites
K Grzegorzewski, KL Komschlies, M Mori, K Kaneda, N Usui, CR Faltynek, JR Keller, FW Ruscetti and RH Wiltrout
Biological Carcinogenesis and Development Program, Program Resources,
Inc/DynCorp, Frederick, MD.
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.
Volume 83,
Issue 2,
pp. 377-385,
01/15/1994
Copyright © 1994 by The American Society of Hematology
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