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

TY - JOUR

T1 - Regulation of major histocompatibility complex class II antigens on human alveolar macrophages by granulocyte-macrophage colony-stimulating factor in the presence of glucocorticoids

AU - Caulfield, J J

AU - Fernandez, M H

AU - Sousa, A R

AU - Lane, S J

AU - Lee, T H

AU - Hawrylowicz, C M

PY - 1999/9

Y1 - 1999/9

N2 - 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.

AB - 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.

KW - Adult

KW - Antigen Presentation

KW - Asthma

KW - Dexamethasone

KW - Fluorescent Antibody Technique

KW - Glucocorticoids

KW - Granulocyte-Macrophage Colony-Stimulating Factor

KW - HLA-DP Antigens

KW - HLA-DQ Antigens

KW - HLA-DR Antigens

KW - Histocompatibility Antigens Class II

KW - Humans

KW - Interferon-gamma

KW - Macrophage Activation

KW - Macrophages, Alveolar

KW - Monocytes

U2 - 10.1046/j.1365-2567.1999.00862.x

DO - 10.1046/j.1365-2567.1999.00862.x

M3 - Article

C2 - 10469240

SN - 0019-2805

VL - 98

SP - 104

EP - 110

JO - Immunology

JF - Immunology

IS - 1

M1 - N/A

ER -