Interactions between products of the mouse W locus, which encodes the c-kit tyrosine kinase receptor, and theSI locus, which encodes a ligand for c-kit receptor, which we have designated stem cell factor (SCF), have a critical role in the development of mast cells. Mice homozygous for mutations at either locus exhibit several phenotypic abnormalities including a virtual absence of mast cells. Moreover, the c-kit ligand SCF can induce the proliferation and maturation of normal mast cells in vitro or in vivo, and also can result in repair of the mast cell deficiency of Sl/Sld amice in vivo. We now report that administrationof SCF intradermally in vivo results in dermal mast cell activation and a mast cell-dependent acute inflammatory response. This effect is c-kit receptor dependent, in that it isnot observed when SCF is administered to mice containing dermal mastcells expressing functionally inactive c-kit receptors, is observed with both glycosylated and nonglycosylated forms ofSCF, and occurs at doses of SCF at least 10-fold lower ona molar basis than the minimally effective dose of the classical dermal mast cell-activating agent substance P. These findings represent the first demonstration in vivo that a c-kit ligand can result in the functional activationof any cellular lineage expressing the c-kit receptor, and suggestthat interactions between the c-kit receptor and itsligandmay influence mast cell biology through complex effects on proliferation, maturation, and function.
ASJC Scopus subject areas
- Immunology and Allergy