EOTAXIN-INDUCED EOSINOPHIL MIGRATION IN THE PERITONEAL-CAVITY OF OVALBUMIN-SENSITIZED MICE - MECHANISM OF ACTION

Cell accumulation in response to i.p. administration of the C-C chemok ine, eotaxin, was studied in vivo. OVA-sensitized mice, exhibiting blo od eosinophilia, had greater eosinophil (E-o) accumulation in response to 500 ng of eotaxin at 6 h (vehicle-injected, 3.0 +/- 0.5 x 10(5); e otaxin-injected, 8.6 +/- 1.0 x 10(5)) than nonsensitized, eotaxin-inje cted mice (2.5 +/- 0.4 x 10(5)). A nonspecific neutrophil migration wa s observed in both vehicle- and eotaxin-injected cavities, The number of intact mast cells in the peritoneal lavages after eotaxin injection was significantly lower than that in vehicle-injected animals (0.8 +/ - 0.3 x 10(4) VS 2.8 +/- 0.6 x 10(4), respectively). When endogenous p eritoneal mast cells were depleted with compound 48/80 before eotaxin administration, there was a 51% reduction in E-o accumulation, This su ggests an important role for endogenous mast cells in mediating the ac tions of eotaxin, The potential role of mast cell mediators in the act ions of eotaxin was also investigated, Pretreatment with histamine-H-1 or serotonin antagonists reduced Es migration in response to eotaxin by 50 to 65%, Furtheu, following pretreatment with a specific mAb agai nst TNF-alpha, only nonspecific neutrophil influx was attenuated. Usin g neutralizing mAbs, Eo migration was found to he dependent on the adh esion molecules P- and E-selectin and CD11b. E-o accumulation was also sensitive to dexamethasone, with doses as low as 0.2 mg/kg inducing 1 00% inhibition, This study provides useful insight into the mechanisms of action of eotaxin.