Granulocyte-macrophage colony-stimulating factor overrides the immunosuppressive function of corticosteroids on rat pulmonary dendritic cells

Abstract

Pulmonary dendritic cells (DC) are present in extremely small numbers, but they are the most potent antigen-presenting cells in the lungs. Pure populations of DC can be isolated from the lung following collagen digestion, Percoll gradient centrifugation, removal of phagocytic cells and flow cytometric sorting for cells which exhibit high levels of surface major histocompatibility complex (MHC) class II molecules. Exogenous GM-CSF enhances this immunostimulatory capacity of the pulmonary DC. Soluble factors produced by type H airway epithelial cells and interstitial macrophages also enhance the immunostimulating capacity of pulmonary DC while alveolar macrophages suppress it. Thus, the function of DC may be regulated by locally produced cytokines. Corticosteroids are widely used as immunosuppressive agents in pharmacotherapy. While these agents are known to inhibit T cell proliferation and macrophage activation, their effects on DC are not known. We found that dexamethasone (Dex) pretreatment resulted in about a 50% reduction in the immunostimulatory capacity of rat pulmonary DC. This was associated with downregulation of MHC class II (Ia) expression. Dex-induced suppression of DC function could be restored with GM-CSF. We conclude that corticosteroids downregulate antigen-presenting capacity by direct suppression of pulmonary DC. This immunosuppressive effect of corticosteroids on DC may, however, be abrogated by exogenous GM-CSF. Corticosteroids and GM- CSF are therapeutic agents with potent direct immunomodulating effects on DC.