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Macrophage-inflammatory protein protects multipotent hematopoietic cells
from the cytotoxic effects of hydroxyurea in vivo
BI Lord, TM Dexter, JM Clements, MA Hunter and AJ Gearing
CRC Department of Experimental Haematology, Paterson Institute for Cancer
Research, Christie Hospital NHS Trust, Manchester, UK.
Macrophage inflammatory protein-1 alpha (MIP-1 alpha) has been assessed for
its potential in vivo to protect hematopoietic progenitor cells from the
cytotoxic effects of a cycle-specific drug--in this case hydroxyurea (HU).
Two doses of HU, 7 hours apart, were administered to mice to induce spleen
colony-forming unit (CFU-S) cycling and then to kill them during
DNA-synthesis. MIP-1 alpha, in a variety of dose and time combinations, was
injected before the second dose of HU in an attempt to prevent recruitment
or maintain CFU-S quiescence, and thus protect them from the second dose of
HU. Without MIP-1 alpha, recovery of the CFU-S population was complete in 7
days. In a dose-dependent manner, MIP-1 alpha either reduced the initial
kill and accelerated recovery, or completely protected the CFU-S
population. We conclude that MIP-1 alpha does protect multipotent
progenitor cells in vivo and that these observations provide a base from
which to build practical clinical applications.
Volume 79,
Issue 10,
pp. 2605-2609,
05/15/1992
Copyright © 1992 by The American Society of Hematology
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