HUMAN SKIN SCID MOUSE CHIMERAS AS AN IN-VIVO MODEL FOR HUMAN CUTANEOUS MAST-CELL HYPERPLASIA

Human skin xenografted to mice with severe combined immunodeficiency s yndrome (SCID) was evaluated to determine the integrity and fate of hu man dermal mast cells, There was an approximately 3-fold increase in n umber of dermal mast cells by 3 mo after engraftment (p < 0.05). These cells were responsive to conventional mast cell secretagogues and wer e confirmed to be of human origin by ultrastructural characterization of granule substructure and by reactivity for the human mast cell prot einase, chymase. CD1a+ Langerhans cells, also bone marrow-derived cell s, failed to show evidence of concomitant hyperplasia, and increased m ast cell number was not associated with alterations in number of derma l vascular profiles identified immunohistochemically for human CD31. R T-PCR analysis demonstrated human but not murine stem cell factor (SCF ; also termed mast cell growth factor, c-kif ligand) mRNA in xenograft s, Epidermal reactivity for stem cell factor protein shifted from a cy toplasmic pattern to an intercellular pattern by 3 mo after engraftmen t, suggesting a secretory phenotype, as previously documented for huma n cutaneous mastocytosis, The majority (>90%) of mast cells demonstrat ed membrane reactivity for human SCF at the time points of peak hyperp lasia. These data establish SCID mouse recipients of human skin xenogr afts as a potential in vivo model for cutaneous mast cell hyperplasia.