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Interleukin-8 induces rapid mobilization of hematopoietic stem cells with
radioprotective capacity and long-term myelolymphoid repopulating ability
L Laterveer, IJ Lindley, MS Hamilton, R Willemze and WE Fibbe
Department of Hematology, University Medical Center Leiden, The
Netherlands.
Interleukin-8 (IL-8) belongs to a family of chemoattractant cytokines
involved in chemotaxis and activation of neutrophils. As in vivo
administration of IL-8 induces granulocytosis and the release of immature
white blood cells into the circulation, we assessed a possible mobilizing
effect of IL-8 on myeloid progenitor cells. IL-8 was administered at
intraperitoneal doses ranging from 0.1 to 100 micrograms per mouse to
female Balb/C mice (aged 8 to 12 weeks; weight, 20 to 25 g). Animals were
killed at time intervals ranging from 1 to 240 minutes after IL-8
administration, and blood, bone marrow, and spleen cells were harvested.
Injection of 30 micrograms IL-8 resulted in an increment from 25 +/- 9 to
418 +/- 299 granulocyte-macrophage colony-forming units (CFU-GM) per
milliliter blood at 15 minutes after a single intraperitoneal injection.
Sixty minutes after the injection of IL-8, the numbers of circulating
CFU-GM per milliliter blood had almost returned to pretreatment values (82
+/- 39 CFU-GM per milliliter). A dose of 100 micrograms IL-8 per animal did
not result in a further increment in the number of circulating CFU-GM.
Transplantation of 5 x 10(5) blood-derived mononuclear cells (MNC) obtained
at 30 minutes after IL-8 injection (30 micrograms) resulted in 69% survival
of lethally irradiated (8.5 Gy) recipients at 60 days versus 22% for
animals transplanted with an equal number of nonprimed blood-derived MNC.
Transplantation of 1.5 x 10(6) MNC obtained from IL- 8-treated donors
resulted in 100% survival. Six months after transplantation, female
recipients of MNC derived from IL-8-treated male donors were killed, and
chimerism was determined in bone marrow, spleen, and thymus using a Y
chromosome-specific probe and fluorescent in situ hybridization (FISH). The
majority of bone marrow, spleen, and thymus cells (83% +/- 25%, 89% +/- 5%,
and 64 +/- 28%, respectively) consisted of Y chromosome-positive cells,
showing that the IL-8- mobilized cells had myelolymphoid repopulating
ability. We conclude that IL-8 is a cytokine that induces rapid
mobilization of progenitor cells and pluripotent stem cells that are able
to rescue lethally irradiated mice and that are able to completely and
permanently repopulate host hematopoietic tissues.
Volume 85,
Issue 8,
pp. 2269-2275,
04/15/1995
Copyright © 1995 by The American Society of Hematology
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