Macrophage-inflammatory protein protects multipotent hematopoietic cells from the cytotoxic effects of hydroxyurea in vivo

Abstract

Macrophage inflammatory protein-1α (MIP-1α) 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-1α, 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-1α, recovery of the CFU-S population was complete in 7 days. In a dose-dependent manner, MIP-1α either reduced the initial kill and accelerated recovery, or completely protected the CFU-S population. We conclude that MIP-1α does protect multipotent progenitor cells in vivo and that these observations provide a base from which to build practical clinical applications. © 1992 by The American Society of Hematology.