INDUCTION OF E-SELECTIN-DEPENDENT LEUKOCYTE RECRUITMENT BY MAST-CELL DEGRANULATION IN HUMAN SKIN-GRAFTS TRANSPLANTED ON SCID MICE

Previous in vitro data indicate that degranulation of human mast cells triggers the induction of endothelial molecules important in leukocyt e adhesion. In vivo experimental systems have not previously existed, however, to determine whether human mast cell degranulation is suffici ent stimulus for leukocyte recruitment. To study this question, neonat al foreskins were transplanted onto immunodeficient mice. The grafts c ontained physiological numbers of human dermal mast cells that could b e degranulated by a number Of secretagogues that activate mast cells b y different mechanisms. Degranulation was associated with an inflammat ory response characterized by, edema, up-regulation primarily of micro vessel E-selectin, and influx of neutrophils. Leukocyte emigration ass ociated with mast cell degranulation was inhibited by a monoclonal ant ibody against human E-selectin These data indicate that degranulation of human mast cells in the human/SCID mouse model provokes cellular in flammation in skin The ability to significantly inhibit early leukocyt e infiltration with an antibody against E-selectin in this model suppo rts the hypothesis that this molecule plays an important role in mast- cell-induced inflammation.