Macrophage-inflammatory protein protects multipotent hematopoietic cells from the cytotoxic effects of hydroxyurea in vivo.
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.
Lord
B I
BI
CRC Department of Experimental Haematology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Dexter
T M
TM
Clements
J M
JM
Hunter
M A
MA
Gearing
A J
AJ
D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D002478:Cells, Cultured; D054407:Chemokine CCL4; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000494:pharmacology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D006918:Hydroxyurea / Q000633:toxicity*; D007700:Kinetics; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D008815:Mice, Inbred Strains; D015846:Monokines / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
D054407:Chemokine CCL4; D016207:Cytokines; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D011994:Recombinant Proteins; D006918:Hydroxyurea