Bactericidal/Permeability-Increasing Protein Inhibits Induction of Macrophage Nitric Oxide Production by Lipopolysaccharide

A recombinant (r) NH2-terminal fragment of bactericidal/permeability-increasing protein, rBPI23, was shown to inhibit murine macrophage nitric oxide (NO) production elicited by lipopolysaccharide (LPS) plus interferon-β (IFN-β). Normal mouse plasma amplified NO synthesis (measured as NO-2 release) at LPS concentrations of 1–10 ng/mL, and antibody to the plasma LPS-binding protein (LBP) partially inhibited N02 release in the presence of normal mouse plasma. rBPI23 (1 µg/mL) effectively inhibited LPS-dependent NO-2 release in the presence or absence of normal mouse plasma. Fifty percent inhibition of IFN-β/LPS-elicited NO-2 production or of binding of fluoresceinated LPS was obtained with ∼0.2 µg/mL rBPI23. These results provide a basis for studies of rBPI23 effects on NO synthase activity in murine models of gramnegative sepsis.