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

Journal Article · Tue Mar 31 23:00:00 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), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:8; ISSN PNASA
• Country of Publication: United States
• Language: English

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