Reversible expansion of primate mast cell populations in vivo by stem cell factor.

Abstract

Mast cell development in mice is critically regulated by stem cell factor (SCF), the term used here to designate a product of fibroblasts and other cell types that is a ligand for the tyrosine kinase receptor protein encoded by the proto-oncogene c-kit. However, the factors which regulate the size of mast cell populations in primates are poorly understood. Here we report that the subcutaneous administration of recombinant human SCF (rhSCF) to baboons (Papio cynocephalus) or cynomolgus monkeys (Macaca fascicularis) produced a striking expansion of mast cell populations in many anatomical sites, with numbers of mast cells in some organs of rhSCF-treated monkeys exceeding the corresponding values in control monkeys by more than 100-fold. Animals treated with rhSCF did not exhibit clinical evidence of mast cell activation, and discontinuation of treatment with rhSCF resulted in a rapid decline of mast cell numbers nearly to baseline levels. These findings are the first to demonstrate that a specific cytokine can regulate mast cell development in primates in vivo. They also provide the first evidence, in any mammalian species, to indicate that the cytokinedependent expansion of tissue mast cell populations can be reversed when administration of the cytokine is discontinued. (J.

Glucocorticoids decrease tissue mast cell number by reducing the production of the c-kit ligand, stem cell factor, by resident cells: in vitro and in vivo evidence in murine systems.

“…Withdrawal of SCF from SCFdependent mast cell cultures in vitro results in apoptosis (19,20), and administration of SCF in vivo in both murine and human studies leads to both local and systemic mast cell hyperplasia (21)(22)(23). Therefore, we hypothesized that glucocorticoids affect mast cell number in tissues by regulating SCF production by cells in the microenvironment.…”

Effects of chronic treatment with the c-kit ligand, stem cell factor, on immunoglobulin E-dependent anaphylaxis in mice. Genetically mast cell-deficient Sl/Sld mice acquire anaphylactic responsiveness, but the congenic normal mice do not exhibit augmented responses.

“…SCF not only influences mast cell development and function in rodents, but also in humans and other primates. Administration of recombinant human SCF (rhSCF) subcutaneously to baboons (Papio species) or cynomolgus monkeys (Macaca fascicularis) in vivo induces mast cell hyperplasia in many anatomical sites (20). rhSCF also can promote the development of human mast cells in vitro, particularly when rhSCF is used as the only exogenous cytokine (21)(22)(23)(24).…”

Stem Cell Factor Has a Suppressive Activity to IgE-Mediated Chemotaxis of Mast Cells

“…In addition to these potentiating effects, SCF has a potential to control mast cell numbers at the peripheral tissues. Daily injection with SCF is capable of inducing mast cells hyperplasia (39), which is reversed when the administration of SCF is discontinued (40). The large amount of soluble SCF compensates for the reduction of mast cell numbers caused by the low expression of c-kit, the receptor of SCF (41).…”