Reversible expansion of primate mast cell populations in vivo by stem cell factor.
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 cytokine-dependent expansion of tissue mast cell populations can be reversed when administration of the cytokine is discontinued.
Galli
S J
SJ
Department of Pathology, Beth Israel Hospital, Boston, Massachusetts 02215.
Iemura
A
A
Garlick
D S
DS
Gamba-Vitalo
C
C
Zsebo
K M
KM
Andrews
R G
RG
D000818:Animals; D004334:Drug Administration Schedule; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects; D016298:Hematopoietic Cell Growth Factors / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007279:Injections, Subcutaneous; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects; D007583:Jejunum / Q000166:cytology / Q000187:drug effects; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects; D008252:Macaca fascicularis; D008407:Mast Cells / Q000166:cytology* / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects; D009928:Organ Specificity; D010215:Papio; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D019089:Stem Cell Factor; D013270:Stomach / Q000166:cytology / Q000187:drug effects; D014132:Trachea / Q000166:cytology / Q000187:drug effects
D016298:Hematopoietic Cell Growth Factors; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011994:Recombinant Proteins; D019089:Stem Cell Factor