Relative concentrations of endotoxin-binding proteins in body fluids during infection.

Abstract

Endotoxin initiates the systemic inflammatory response, haemodynamic changes, and multi-organ failure that may occur as a consequence of systemic gram-negative bacterial infection. The serum protein lipopolysaccharide-binding protein (LBP) binds to the lipid A component of bacterial endotoxin and facilitates its delivery to the CD14 antigen on the macrophage, where inflammatory cytokines are released and a cascade of host mediators is initiated. The neutrophil granular protein bactericidal/permeability-increasing protein (BPI) competes with LBP for endotoxin binding and functions as a molecular antagonist of LBP-endotoxin interactions. We have measured concentrations of both proteins in body fluids from 49 consecutive patients. In 16 of 17 samples of fluid from closed-space infections, BPI was present in greater concentration than LBP (median BPI/LBP ratio 7.6 [95% CI 2.32-22.1]). The ratio of BPI and LBP was not significantly different from 1.0 in abdominal fluid from 10 patients with peritonitis (ratio 0.235 [0.18-0.47]), whereas the BPI/LBP ratio was low in 22 non-infected body fluids (0.01 [0.001-0.04]) and concentrations of both proteins approached those in normal human plasma. BPI concentrations were directly correlated with the quantity of neutrophils within clinical samples (rs = 0.81, p < 0.0001). Thus, within abscess cavities BPI is available in sufficient quantities for effective competition with LBP for endotoxin. BPI may attenuate the local inflammatory response and the systemic toxicity of endotoxin release during gram-negative infections.

• Authors: S M Opal, J E Palardy, M N Marra, C J Fisher Jr, B M McKelligon, R W Scott
• Journal: Lancet (London, England) (Lancet) Vol. 344 Issue 8920 Pg. 429-31 (Aug 13 1994) ISSN: 0140-6736 [Print] England
• PMID: 7520106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acute-Phase Proteins
• Antimicrobial Cationic Peptides
• Blood Proteins
• Carrier Proteins
• Membrane Glycoproteins
• Membrane Proteins
• bactericidal permeability increasing protein
• lipopolysaccharide-binding protein

Topics

• Abscess (immunology, microbiology, pathology)
• Acute-Phase Proteins
• Aged
• Antimicrobial Cationic Peptides
• Bacterial Infections (immunology, microbiology, pathology)
• Binding, Competitive
• Blood Bactericidal Activity
• Blood Proteins (analysis, chemistry, immunology)
• Body Fluids (chemistry)
• Carrier Proteins (analysis, chemistry, immunology)
• Female
• Humans
• Inflammation
• Male
• Membrane Glycoproteins
• Membrane Proteins
• Middle Aged
• Neutrophils
• Peritonitis (immunology, microbiology, pathology)
• Permeability