Regulation of dendritic cell recruitment into resting and inflamed airway epithelium: Use of alternative chemokine receptors as a function of inducing stimulus

Dendritic cells (DC) were purified by flow cytometry from rat tracheal muco sa; they exhibited the phenotypic characteristics of immature DC including high endocytic activity, low CD80/86 expression, and in vitro responsivenes s to a broad range of CC chemokines. Daily treatment of adult rats with the selective CCR1 and CCR5 antagonist Met-RANTES reduced baseline numbers of tracheal intraepithelial DC by 50-60%, and pretreatment of animals with Met -RANTES before inhalation of aerosol containing heat-killed bacteria abolis hed the rapid DC influx into the epithelium that occurred in untreated cont rols, implicating CCR1 and CCR5 and their ligands in recruitment of immatur e DC precursors into resting airway tissues and during acute bacterial-indu ced inflammation. Comparable levels of DC recruitment were observed during airway mucosal Sendai virus infection and after aerosol challenge of sensit ized animals with the soluble recall Ag OVA. However, Met-RANTES did not af fect these latter responses, indicating the use of alternative chemokine re ceptors/ligands for DC recruitment, or possibly attraction of different DC subsets, depending on the nature of the eliciting stimulus.