THE ROLE OF MAST CELL-DERIVED HISTAMINE IN THE CLOSURE OF AN IN-VITROWOUND

We have previously reported that mast cells (MC) stimulate 3T3 fibrobl ast migration and proliferation into an in vitro model of wound obtain ed by producing in a confluent 3T3 monolayer, a midline cut and by scr aping the cells from half of the monolayer. The purpose of the present study was to determine the contribution of mast cell-derived histamin e to this MC increasing effect. Histamine levels in supernatants of MC /3T3 cultures unactivated or activated with either compound 48/80 or a nti-IgE antibodies (10 min) did not correlate to the degree of fibrobl ast migration and proliferation into the wound space (42 h). Various c oncentrations of histamine were added to 3T3 fibroblast monolayers in the absence of cocultured MC, and fibroblasts beyond the wound line we re counted (42 h). Addition of 100 ng/ml histamine had the highest sti mulating effect on fibroblast numbers. This effect was abrogated by th e addition of cimetidine (an H-2 antagonist). Addition of cimetidine t o unactivated MC/3T3 cultures did not affect the increasing activity o f MC presence on the wounded monolayer, although it diminished the enh ancing effect obtained after MC activation with compound 48/80. These results indicate that histamine is partially responsible for the mast cell enhancing effect on fibroblast migration and proliferation in an in vitro model of wound.