In vivo stimulation of granulopoiesis by recombinant human granulocyte colony-stimulating factor

Journal Article · Wed Apr 01 00:00:00 EST 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.8.2484· OSTI ID:6072281

Cohen, A M; Zsebo, K M; Inoue, H; Hines, D; Boone, T C; Chazin, V R; Tsai, L; Ritch, T; Souza, L M

Osmotic pumps containing Escherichia coli-derived recombinant human granulocyte colony-stimulating factor (rhG-CSF) were attached to indwelling jugular vein catheters and implanted subcutaneously into Golden Syrian hamsters. Within 3 days, peripheral granulocyte counts had increased > 10-fold with a concomitant 4-fold increase in total leukocytes. Microscopic examination of Wright-Giemsa-stained blood smears from rhG-CSF hamsters showed that only the neutrophil subpopulation of granulocytes had increased. After subcutaneous injection at /sup 35/S-labeled rhG-CSF doses of up to 10 ..mu..g x kg/sup -1/ x day/sup -1/ only granulocyte counts were affected. However, at higher dose levels, a transient thrombocytopenia was noted. Erythrocyte and lymphocyte/monocyte counts remained unaffected by rhG-CSF over the entire dose range studied. Total leukocyte counts increased 3-fold within 12 hr after a single s.c. injection of rhG-CSF. This early effect was associated with an increase in the total number of colony-forming cells and the percent of active cycling cells in the marrow. A sustained elevation of peripheral leukocyte and marrow progenitor counts was observed following seven daily s.c. injections of rhG-CSF. The ability of rhG-CSF to increase the production and release of granulocytes from the marrow may underlie the beneficial effect it produced on the restoration of peripheral leukocyte counts in hamsters made leukopenic by treatment with 5-fluorouracil.

• Research Organization: Amgen, Thousand Oaks, CA
• OSTI ID: 6072281
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Vol. 84:8
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
GLUCOPROTEINS
BLOOD-PLASMA CLEARANCE
LABELLED COMPOUNDS
LEUKOPOIESIS
STIMULATION
BLOOD COUNT
BONE MARROW
CYSTEINE
GROWTH
HAMSTERS
IN VIVO
METHIONINE
SULFUR 35
VEINS
AMINO ACIDS
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BLOOD FORMATION
BLOOD VESSELS
BODY
CARBOHYDRATES
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
CLEARANCE
DAYS LIVING RADIOISOTOPES
DRUGS
EVEN-ODD NUCLEI
HEMATOPOIETIC SYSTEM
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
MAMMALS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PROTEINS
RADIOISOTOPES
RODENTS
SACCHARIDES
SULFUR ISOTOPES
THIOLS
TISSUES
VERTEBRATES
550301* - Cytology- Tracer Techniques