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-gamma (IFN-gamma). Normal mouse plasma amplified NO synthesis (measured as NO2- release) at LPS concentrations of 1-10 ng/mL, and antibody to the plasma LPS-binding protein (LBP) partially inhibited NO2- release in the presence of normal mouse plasma. rBPI23 (1 microgram/mL) effectively inhibited LPS-dependent NO2- release in the presence or absence of normal mouse plasma. Fifty percent inhibition of IFN-gamma/LPS-elicited NO2- production or of binding of fluoresceinated LPS was obtained with approximately 0.2 microgram/mL rBPI23. These results provide a basis for studies of rBPI23 effects on NO synthase activity in murine models of gram-negative sepsis.
Corradin
S B
SB
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Heumann
D
D
Gallay
P
P
Smith
J
J
Mauël
J
J
Glauser
M P
MP
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001770:Blood Bactericidal Activity / Q000187:drug effects*; D001798:Blood Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D018313:Leishmania enriettii / Q000502:physiology; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000469:parasitology; D008565:Membrane Proteins; D051379:Mice; D008808:Mice, Inbred CBA; D009569:Nitric Oxide / Q000096:biosynthesis*; D010539:Permeability; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C021623:bactericidal permeability increasing protein; D009569:Nitric Oxide; D007371:Interferon-gamma