Abstract
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.
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