Modulation of MHC class II transport and lysosome distribution by macrophage-colony stimulating factor in human dendritic cells derived from monocytes.
The macrophage-colony stimulating factor (M-CSF) has been already shown to affect the function of dendritic cells (DC). Therefore, the differentiation of dendritic cells into macrophages (M(PHI)) might represent a pathway which could inhibit the immune response initiated by DC. Because Major Histocompatibility Complex class II molecules (MHC-II) are crucial for DC function, we asked whether M-CSF may influence the intracellular transport of MHC-II in monocyte derived DC. We found that, at early stages, M-CSF induced first a rapid redistribution of MHC-II from the MHC-II containing compartments (MIIC) to the plasma membrane and second an increase in MHC-II synthesis as observed with LPS or TNF-(alpha). These processes were associated with the sorting of MHC-II from lysosomal membranes which underwent a drastic structural reorganization. However, in contrast to tumor necrosis factor (TNF)-(alpha) or lipopolysaccharide (LPS), M-CSF neither potentiated the allostimulatory function of DC nor allowed the stabilization of MHC-II at the cell surface, but rather increased MHC-II turnover. We conclude that the rapid modulation of MHC-II transport and distribution may participate in the inhibitory effect of M-CSF on DC function and differentiation.
Baron
C
C
UMR 144 CNRS-Institut Curie, Laboratoire des Mécanismes Moléculaires du Transport Intracellulaire, rue d'Ulm, Paris, France.
Raposo
G
G
Scholl
S M
SM
Bausinger
H
H
Tenza
D
D
Bohbot
A
A
Pouillart
P
P
Goud
B
B
Hanau
D
D
Salamero
J
J
D015703:Antigens, CD / Q000378:metabolism; D002469:Cell Separation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D000949:Histocompatibility Antigens Class II / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D016253:Microscopy, Immunoelectron; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D060149:Tetraspanin 30
D015703:Antigens, CD; C554586:CD63 protein, human; D000949:Histocompatibility Antigens Class II; D010980:Platelet Membrane Glycoproteins; D060149:Tetraspanin 30; D016173:Macrophage Colony-Stimulating Factor