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

Medical Service, VA Medical Center and Albany Medical College, Albany, New York 12208 [G. C.]; Departments of Medicine (Hematology/Oncology) [H. E. B., S. C., D. E. W., G. H.], Microbiology and Immunology [H. E. B.], and the Walther Oncology Center, Indiana University School of Medicine [H. E. B.], Indianapolis, Indiana 46202; Department of Medicine, Mt. Sinai School of Medicine, New York, New York 10029 [M. L. G.]; and Department of Medicine, Montefiore Hospital, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania [A. W., R. K. S.]

Hematopoietic efficacy in vivo of multiple injections of purified murine L-cell and recombinant human macrophage colony-stimulating factors (M-CSF; specific activity, > 2 x 10⁷ units/mg) was assessed in mice. Injections i.v. of sterile saline or 20,000 units of M-CSF were administered 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 F₁ mice. Numbers and cycling rates of marrow and spleen granulocyte-macrophage, erythroid, and multipotential progenitor 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 progenitors.

¹ These studies were performed during the sabbatical leave of G. C. at the Indiana University School of Medicine and were supported by the VA Merit Review Program (to G. C.), by Public Health Service Grants CA 36464 and CA 36740 (to H. E. B.), by Grant CA 15237 (to R. K. S.) from the National Cancer Institute, and by a grant from the Cetus Corporation (to H. E. B.).

² To whom requests for reprints should be addressed, at VA Medical Center, 111J, 113 Holland Avenue, Albany, NY 12208.

³ Supported by NIH Training Program IT 32 AM-07519. Present address: Immunex Corporation, Seattle, WA.

Received 7/18/88. Revised 11/28/88. Revised 3/23/89. Accepted 4/ 4/89.