Single and Combination Cytokine Therapies for Treatment of Radiation- Induced Hematopoietic Injury: Effects of c-kit Ligand and Interleukin-3
Abstract
One of the most recent cytokines implicated in hematopoietic regulation is c-kit ligand, also known as mast cell growth factor (MGF), steel factor (SLF), and stem cell factor (SCF) (1-3). The c-kit ligand has been ascribed numerous hematopoietic and nonhematopoietic effects, although it was initially identified and purified based on its ability to stimulate mast cell growth (2-5). Multiple studies have focused on the in vitro effects of this factor, demonstrating that alone is has limited hematopoietic activity, but when combined with other hematopoietic cytokines, it synergizes to increase both the number and size of colonies generated from hematopoietic progenitors (3-11), and in some instance, to combination with such factors, c-kit ligand also synergistically enhances the in vitro expansion of hematopoietic progenitors grown in liquid cultures (13-15. These effects are thought to result not only from the ability fo c-kit ligand to potentiate progenitor cell proliferation but also from its ability to enhance progenitor cell survival (14,16). IL-3, also known as multi-CSF, has previously been shown to enhance hematopoietic regeneration in irradiated animals based on recovery of peripheral blood white cells and platelets (17). Because in vitro studies have demonstrated synergistic hematopoietic stimulation produced by c-kit ligand combined with IL-3, we evaluated whether co-administration of these cytokines in vivo would synergize to further accelerate hematopoietic regeneration following radiation-induced hematopoietic hypoplasia
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 1994
- Accession Number
- ADA280461
Entities
People
- Dana Williams
- F. Seiler
- M. L. Patchen
- R. Fischer
- T. J. Macvittie
Organizations
- Armed Forces Radiobiology Research Institute