Modulation of interferon-gamma-induced major histocompatibility (MHC) and CD14 antigen changes by lipophilic muramyltripeptide MTP-PE in human monocytes.
The lipophilic muramylpeptide derivative muramyltripeptide-phosphatidylethanolamine (MTP-PE, 0.05 to 5 micrograms/ml) and human recombinant interferon-gamma (rIFN-gamma, 1 to 100 U/ml) were applied singly or in combination to fresh human mononuclear blood leucocytes in vitro. After 15 to 72 hr incubation, culture- and drug-induced changes in beta 2-microglobulin (MHC class I associated), HLA-DR (MHC class II), and Leu-M3 (CD14) antigen expression were investigated by flow cytometry; changes in monocyte morphology (forward light scatter and side scatter) were assessed by scatter analysis. It was found that (1) rIFN-gamma caused a simultaneous down-regulation of the CD14 antigen and an up-regulation of MHC class I and class II molecules on the surface of cultured monocytes; (2) MTP-PE, which by itself failed to influence the expression of these antigens, synergized with rIFN-gamma in increasing MHC antigens and reducing CD14; (3) at high concentrations rIFN-gamma reduced monocyte viability to a small but significant extent and this effect was further potentiated by MTP-PE; and (4) untreated monocytes in culture showed an apparently MTP-PE-insensitive increase in size, density, and beta 2-microglobulin, HLA-DR, and CD14 antigen expression. The influence of MTP-PE on rIFN-gamma-induced surface marker changes may contribute to its immunoadjuvant activity in vivo.
Landmann
R
R
Department of Research, University Hospital, Basel, Switzerland.
Wesp
M
M
Dukor
P
P
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors; D009000:Monocytes / Q000276:immunology*; D010714:Phosphatidylethanolamines / Q000494:pharmacology*; D011994:Recombinant Proteins; D013997:Time Factors; D001613:beta 2-Microglobulin / Q000378:metabolism
D015214:Antigens, Differentiation, Myelomonocytic; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D010714:Phosphatidylethanolamines; D011994:Recombinant Proteins; D001613:beta 2-Microglobulin; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma