Lipopolysaccharide effectively up-regulates B7-1 (CD80) expression and costimulatory function of human monocytes

Area of Science:

• Immunology
• Cell Biology

Background:

• Human monocytes express key surface molecules like ICAM-1, LFA-3, and HLA-DR.
• B7-1, a critical costimulatory molecule, is typically absent on resting monocytes.

Purpose of the Study:

• To investigate how lipopolysaccharide (LPS) and cytokines affect B7-1, ICAM-1, LFA-3, and HLA-DR expression on human monocytes.
• To determine the impact of these molecular changes on monocyte costimulatory function.

Main Methods:

• Freshly isolated human monocytes were treated with LPS and various cytokines.
• Expression levels of B7-1, ICAM-1, LFA-3, and HLA-DR were analyzed.
• Monocyte costimulatory function was assessed using a tetanustoxoid (TT) assay.
• Blocking experiments with CTLA-4Ig were performed.

Main Results:

• LPS significantly upregulated B7-1 expression on monocytes; interferon-gamma (IFN-γ) had a lesser effect.
• IFN-γ and LPS also upregulated ICAM-1 and HLA-DR, while LFA-3 remained unchanged.
• LPS markedly enhanced monocyte costimulatory function in the TT assay.
• CTLA-4Ig blockade almost completely abolished the LPS-induced enhancement of costimulatory function.

Conclusions:

• The LPS-mediated enhancement of human monocyte costimulatory function is primarily driven by the upregulation of B7-1.
• This B7-1 dependent mechanism is likely vital for effective host defense against Gram-negative bacterial infections.