Regulation of major histocompatibility complex class II antigens on human alveolar macrophages by granulocyte-macrophage colony-stimulating factor in the presence of glucocorticoids.
Alveolar macrophages (AM) present antigen poorly to CD4+ T cells and respond weakly to interferon-gamma (IFN-gamma) for up-regulation of major histocompatibility complex (MHC) class II and costimulatory molecule expression. In atopic asthma, however, AM exhibit enhanced antigen-presenting cell (APC) activity. Since granulocyte-macrophage colony-stimulating factor (GM-CSF) is increased in the airways of asthmatic patients, we have investigated its role in modulating the APC function of AM. The effects of glucocorticoids were also studied since earlier studies showed optimal induction of MHC antigens on monocytes by GM-CSF in their presence. GM-CSF in the presence, but 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 concentration 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.
Caulfield
J J
JJ
Department of Respiratory Medicine and Allergy, King's College London at Guy's Hospital, London, UK.
Fernandez
M H
MH
Sousa
A R
AR
Lane
S J
SJ
Lee
T H
TH
Hawrylowicz
C M
CM
D000328:Adult; D017951:Antigen Presentation / Q000187:drug effects*; D001249:Asthma / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005938:Glucocorticoids / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006682:HLA-DP Antigens / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology*; D009000:Monocytes / Q000276:immunology
D005938:Glucocorticoids; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D003907:Dexamethasone; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor