Because of the mortality associated with Gram-negative infections, there is interest in the mechanisms by which bacterial endotoxin is processed by leukocytes. Several lipid A binding proteins, including lipopolysaccharide-binding protein (LBP) and bactericidal/permeability-increasing protein (BPI), mediate the process of LPS activity. Our studies show that BPI was capable of mediating the binding of tritiated LPS to the mononuclear cell line THP-1 in a fashion not affected by the addition of an anti-CD14 antibody, and that such binding did not elicit a TNFa response. Soluble BPI was capable of competing with LBP for LPS and inhibiting the TNFα response associated with LBP-LPS stimulation. In addition, cells pretreated with BPI and then washed were then capable of binding significantly more LPS than controls. These pretreated cells were also capable of inhibiting TNFα production to subsequent LBP-LPS. Western blotting confirmed the uptake of BPI to THP-1 cells both with and without LPS. We conclude that BPI is capable of interacting with THP-1 cells in the free form or complexed to LPS, without eliciting a TNFα response. Cells exposed to BPI are resistant to subsequent stimulation with LBP-LPS, thereby suggesting a novel mechanism for the anti-inflammatory effects of BPI.
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