Antagonists of CD117 cKit signaling inhibit mast cell accumulation in healing skin wounds

Mast cells MCs have important functional roles in leukocyte recruitment, pain, and wound healing, and increased tissue resident MC function has been associated with several fibrotic diseases. Consequently, the study of MCs in situcan be a direct approach to studying the pharmacodynamic impact of MCdirected therapeutics in tissues. Here we describe an automated laser scanning cytometry assay that was used to characterize the kinetics of MC accumulation in healing skin wounds and to study the effect of inhibiting CD117 cKit signaling. The number of tryptasepositive MCs approximately doubled 14 days after cutaneous injury in nonhuman primates. Treatment of animals with antiCD117 or imatinib mesylate Gleevec® reduced MC accumulation at the edge of healing wounds in mice and nonhuman primates, respectively. In translating this MC assay to become a biomarker for human studies, no differences in dermal MC numbers were evident between genders, ages or body mass index from 20 healthy donors. These data suggest that skin is a practical and useful tissue for tracking pharmacodynamic effects of MCdirected therapies. © 2008 International Society for Advancement of Cytometry