Host Defense Proteins and Peptides with Lipopolysaccharide-Binding Activity from Marine Invertebrates and Their Therapeutic Potential in Gram-Negative Sepsis

Abstract

Sepsis is a life-threatening complication of an infectious process that results from the excessive and uncontrolled activation of the host’s pro-inflammatory immune response to a pathogen. Lipopolysaccharide (LPS), also known as endotoxin, which is a major component of Gram-negative bacteria’s outer membrane, plays a key role in the development of Gram-negative sepsis and septic shock in humans. To date, no specific and effective drug against sepsis has been developed. This review summarizes data on LPS-binding proteins from marine invertebrates (ILBPs) that inhibit LPS toxic effects and are of interest as potential drugs for sepsis treatment. The structure, physicochemical properties, antimicrobial, and LPS-binding/neutralizing activity of these proteins and their synthetic analogs are considered in detail. Problems that arise during clinical trials of potential anti-endotoxic drugs are discussed.

Keywords

• lipopolysaccharide (LPS, endotoxin)
• LPS-binding proteins/peptides
• host defense proteins/peptids
• innate immune system
• marine invertebrates
• Gram-negative sepsis