THE C-KIT LIGAND, STEM-CELL FACTOR, PROMOTES MAST-CELL SURVIVAL BY SUPPRESSING APOPTOSIS

Stem cell factor (SCF) and its receptor (SCFR), a member of the recept or tyrosine kinase III family that is encoded by the c-kit gene, criti cally regulate several complex biological programs including hematopoi esis, mast cell development, cutaneous Pigmentation, and gametogenesis . We show herein that mouse mast cells die rapidly after the withdrawa l of SCF in vivo or in vitro and provide morphological evidence that s uch mast cells undergo programmed cell death or apoptosis. We also sho w that when in vitro-derived mouse mast cells maintained in SCF are re moved from SCF-containing medium for only 5 or 6 hours, the cells' gen omic DNA exhibits the ladderlike pattern of oligonucleosome-sized frag ments typical of apoptosis. These findings demonstrate that SCF can re gulate the survival of a cellular lineage which expresses the SCFR by suppressing apoptosis. They also identify a mechanism that can result in striking and rapid reductions in the size of tissue mast cell popul ations without histological evidence of the concomitant induction of a significant inflammatory response.