Hematopoietic properties of granulocyte colony-stimulating factor/immunoglobulin (G-CSF/IgG-Fc) fusion proteins in normal and neutropenic rodents

Autor: Elizabeth A. Chlipala, George N. Cox, Stacie J. Bell, Sharon J. Carlson, Daniel H. Doherty, Darin J. Smith
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Time Factors
Neutrophils
Cancer Treatment
Gene Expression
lcsh:Medicine
Pharmacology
Biochemistry
Immunoglobulin G
White Blood Cells
Leukocyte Count
Mice
Animal Cells
Bone Marrow
Drug Discovery
Gene Order
Granulocyte Colony-Stimulating Factor
Medicine and Health Sciences
Platelet
lcsh:Science
Immune System Proteins
Multidisciplinary
biology
Hematology
Animal Models
Granulocyte colony-stimulating factor
Haematopoiesis
medicine.anatomical_structure
Oncology
Cytokines
Female
Cellular Types
Research Article
Biotechnology
Neutropenia
Drug Research and Development
Immune Cells
Recombinant Fusion Proteins
Immunology
Cytokine Therapy
Mouse Models
Granulocyte
Research and Analysis Methods
Antibodies
Model Organisms
Hematopoietic Growth Factors
In vivo
medicine
Animals
Blood Cells
lcsh:R
Biology and Life Sciences
Proteins
Cell Biology
Molecular Development
medicine.disease
Fusion protein
Hematopoiesis
Blood Cell Count
Immunoglobulin Fc Fragments
Rats
Disease Models
Animal
Immune System
biology.protein
lcsh:Q
Developmental Biology
Zdroj: PLoS ONE, Vol 9, Iss 3, p e91990 (2014)
PLoS ONE
ISSN: 1932-6203
Popis: Previously we showed that granulocyte colony-stimulating factor (G-CSF) in vitro bioactivity is preserved when the protein is joined via a flexible 7 amino acid linker to an immunoglobulin-1 (IgG1)-Fc domain and that the G-CSF/IgG1-Fc fusion protein possessed a longer circulating half-life and improved hematopoietic properties compared to G-CSF in normal rats. We have extended this analysis by comparing the relative hematopoietic potencies of G-CSF/IgG1-Fc to G-CSF in normal mice and to G-CSF and polyethylene glycol (PEG) - modified G-CSF in neutropenic rats. Mice were treated for 5 days using different doses and dosing regimens of G-CSF/IgG1-Fc or G-CSF and circulating neutrophil levels in the animals measured on Day 6. G-CSF/IgG1-Fc stimulated greater increases in blood neutrophils than comparable doses of G-CSF when administered using daily, every other day or every third day dosing regimens. In rats made neutropenic with cyclophosphamide, G-CSF/IgG1-Fc accelerated recovery of blood neutrophils to normal levels (from Day 9 to Day 5) when administered as 5 daily injections or as a single injection on Day 1. By contrast, G-CSF accelerated neutrophil recovery when administered as 5 daily injections, but not when administered as a single injection. G-CSF/IgG1-Fc was as effective as PEG-G-CSF at accelerating neutrophil recovery following a single injection in neutropenic rats. G-CSF/IgG1-Fc and G-CSF/IgG4-Fc fusion proteins in which the 7 amino acid linker was deleted also were effective at accelerating neutrophil recovery following a single injection in neutropenic rats. These studies confirm the enhanced in vivo hematopoietic properties of G-CSF/IgG-Fc fusion proteins.
Databáze: OpenAIRE
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