RECOMBINANT HUMAN STEM-CELL FACTOR (KIT-LIGAND) PROMOTES HUMAN MAST-CELL AND MELANOCYTE HYPERPLASIA AND FUNCTIONAL ACTIVATION IN-VIVO

Stem cell factor (SCF), also known as mast cell growth factor, kit lig and, and Steel factor, is the ligand for the tyrosine kinase receptor (SCFR) that is encoded by the c-kit proto-oncogene. We analyzed the ef fects of recombinant human SCF (r-hSCF, 5-50 mu g/kg/day, injected sub cutaneously) on mast cells and melanocytes in a phase I study of 10 pa tients with advanced breast carcinoma. A wheal and flare reaction deve loped at each r-hSCF injection site; by electron microscopy, most derm al mast cells at these sites exhibited extensive, anaphylactic-type de granulation. A 14-d course of r-hSCF significantly increased dermal ma st cell density at sites distant to those injected with the cytokine a nd also increased both urinary levels of the major histamine metabolit e, methyl-histamine, and serum levels of mast cell a-tryptase. Five su bjects developed areas of persistent hyperpigmentation at r-hSCF injec tion sites; by light microscopy, these sites exhibited markedly increa sed epidermal melanization and increased numbers of melanocytes. The d emonstration that r-hSCF can promote both the hyperplasia and the func tional activation of human mast cells and melanocytes in vivo has impl ications for our understanding of the role of endogenous SCF in health and disease. These findings also indicate that the interaction betwee n SCF and its receptor represents a potential therapeutic target for r egulating the numbers and functional activity of both mast cells and c utaneous melanocytes.