Regulation of major histocompatibility complex class II antigens on human alveolar macrophages by granulocyte-macrophage colony-stimulating factor inthe presence of glucocorticoids

Alveolar macrophages (AM) present antigen poorly to CD4(+) T cells and resp ond weakly to interferon-gamma (IFN-gamma) for up-regulation of major histo compatibility complex (MHC) class II and costimulatory molecule expression. In atopic asthma, however, AM exhibit enhanced antigen-presenting cell (AP C) activity. Since granulocyte-macrophage colony-stimulating factor (GM-CSF ) is increased in the airways of asthmatic patients, we have investigated i ts role in modulating the APC function of AM. The effects of glucocorticoid s were also studied since earlier studies showed optimal induction of MHC a ntigens on monocytes by GM-CSF in their presence. GM-CSF in the presence, b ut not the absence, of dexamethasone enhanced the expression of HLA-DR, -DP and -DQ antigens by AM. However AM and monocytes differed in the optimal c oncentration of steroid required to mediate this effect (10(-10) M and 10(- 7) M, respectively). Induction of MHC antigens was glucocorticoid specific and independent of IFN-gamma. These studies suggest the existence of an IFN -gamma-independent pathway of macrophage activation, which may be important in regulating APC function within the lung.