Lipopolysaccharide effectively up-regulates B7-1 (CD80) expression and costimulatory function of human monocytes.
The influence of lipopolysaccharide (LPS) and various cytokines on the expression of the costimulatory molecule B7-1 and intercellular adhesion molecule-1 (ICAM-1), lymphocyte function associated antigen-3 (LFA-3) and human histocompatibility leucocyte antigen-DR (HLA-DR) on human monocytes and their effect on the costimulatory function was investigated. Freshly isolated human monocytes constitutively express ICAM-1, LFA-3 and HLA-DR, but no B7-1. B7-1 expression was up-regulated by LPS and, to a lesser extent, by interferon-gamma (IFN-gamma). The other stimuli tested, including IFN-alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor-alpha (TNF-alpha) and GM-CSF+TNF-alpha, did not influence expression of B7-1 on monocytes. ICAM-1 and HLA-DR were up-regulated by IFN-gamma and LPS; LFA-3 expression was not influenced. LPS also effectively enhanced costimulatory function of monocytes as determined in the tetanustoxoid (TT) assay. Blocking of B7 by CTLA-4Ig inhibited the LPS-induced enhancement of costimulatory function almost completely. Our results indicate that the LPS-mediated up-regulation of the costimulatory function of human monocytes is mediated by B7. This mechanism may be important for host defence against Gram-negative bacteria.
Schmittel
A
A
Department of Hematology Oncology, Medizinische Klinik V, University of Heidelberg, Germany.
Scheibenbogen
C
C
Keilholz
U
U
D000069594:Abatacept; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology; D018122:B7-1 Antigen / Q000096:biosynthesis*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018968:CD58 Antigens / Q000096:biosynthesis; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D018796:Immunoconjugates; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D018968:CD58 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006684:HLA-DR Antigens; D018796:Immunoconjugates; D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1; D000069594:Abatacept