Lack of significant skin inflammation during elimination by apoptosis of large numbers of mouse cutaneous mast cells after cessation of treatment with stem cell factor

Abstract

We previously reported that subcutaneous (s.c.) administration of stem cell factor (SCF), the ligand for the c-Kit receptor, to the back skin of mice promotes marked local increases in the numbers of cutaneous mast cells (MCs), and that cessation of SCF treatment results in the rapid reduction of cutaneous MC populations by apoptosis. In the present study, we used the 125I-fibrin deposition assay, a very sensitive method for quantifying increased vascular permeability, to assess whether the clearance of large numbers of apoptotic MCs is associated with significant cutaneous inflammation. The s.c. injection of rrSCF164 (30 or 100 μg/kg/day) or rrSCF164-peg (polyethylene glycol-treated SCF, 30 or 100 μg/kg/day) for 23 days increased the numbers of dermal MCs at skin injection sites from 5.1±0.7 MCs/mm2 to 36.4±4.1, 34.7±9.7, 52.5±5.8, and 545±97 MCs/mm2, respectively. In contrast, MC numbers were markedly lower in mice that had been treated with SCF for 21 days, followed by 2 days of injection with the vehicle alone. Notably, when tested during the period of rapid reduction of skin MCs,125I-fibrin deposition in the skin was very similar to that in mice receiving continuous treatment with SCF or vehicle. We conclude that the rapid elimination of even very large populations of MCs by apoptosis, which also results in the clearance of the considerable quantities of proinflammatory products stored by these cells, does not lead to significant local cutaneous inflammatory responses.