Effect in Vivo of Multiple Injections of Purified Murine and Recombinant Human Macrophage Colony-stimulating Factor to Mice1

Hematopoietic efficacy in vivoof multiple injections of purified murine I -cell and recombinant human macrophage colony-stimulating factors (M-CSF; specific activity, >2 x IO7 units/mg) was assessed in mice. Injections i.v. of sterile saline or 20,000 units of M-CSF were adminis tered once (at 0 h), twice (at 0 and 12 h), or three times (at 0, 12, and 24 h) to C57BL/6 x DBA/2 F, mice. Numbers and cycling rates of marrow and spleen granulocyte-macrophage, erythroid, and multipotential pro genitor cells were assessed 32-36 h after the first injection. Marrow, spleen, and peripheral blood cellularity was assessed at intervals of up to 105 h. Progenitor cell cycling rates were significantly increased after one and two injections of M-CSF but were reduced to a slow or noncycling state after three injections. For marrow cells, the third injection resulted in a significant suppression of hematopoietic progenitor cell cycling compared to the control group. No significant changes were noted for number of progenitors per femur or spleen, for marrow, spleen, or peripheral blood cellularity, or for differential cell counts in these organs after any of the M-CSF treatment schedules. Suppression of progenitor cell proliferation noted after three injections of M-CSF may at least partially explain why repeated injections of 20,000 units of M-CSF fails to increase bone marrow, spleen, or blood cellularity even though one injection of M-CSF increases cycling rates of the hematopoietic progen itors.