In vivo Stimulation of Granulopoiesis by Recombinant Human Granulocyte Colony-Stimulating Factor

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 84; no. 8; pp. 2484 - 2488
• Main Authors: Cohen, Arthur M., Zsebo, Krisztina M., Inoue, Hideo, Hines, Dawn, Boone, Thomas C., Chazin, Vicki R., Tsai, Lawrence, Ritch, Thomas, Souza, Lawrence M.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.04.1987; National Acad Sciences
• Subjects: Animals; Biological and medical sciences; Blood; Bone marrow; Bone Marrow Cells; Cell physiology; Chlorofluorocarbons; Colony stimulating factors; Colony-Forming Units Assay; Cricetinae; Escherichia coli - genetics; Fundamental and applied biological sciences. Psychology; Granulocytes; Granulocytes - cytology; Granulocytes - drug effects; Hamsters; Hematopoiesis - drug effects; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - drug effects; Humans; Interleukin-3 - pharmacology; Kinetics; Leukocyte Count; Leukocytes; Male; Mesocricetus; Mice; Molecular and cellular biology; Progenitor cells; Recombinant Proteins - pharmacology; Responses to growth factors, tumor promotors, other factors; In vivo; Animal; Granulocyte; Bone marrow; Product; Activation; Genetic engineering; Colony stimulating factor; Biological activity; Granulopoiesis
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.84.8.2484

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-Giemsastained blood smears from rhG-CSF hamsters showed that only the neutrophil subpopulation of granulocytes had increased. No significant changes in lymphocyte or monocyte counts were observed during the course of continuous rhG-CSF treatment. After subcutaneous injection at rhG-CSF doses of up to 10 μ g· kg-1· day-1only 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 (0.3-300 μ g· kg-1· day-1) 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.