Bactericidal/Permeability-Increasing Protein (BPI) is a crucial component of the human innate immune system. It is a 456-residue protein with a molecular weight of approximately 50 kDa . BPI is encoded by the BPI gene located on chromosome 20q11.23 . This protein belongs to the family of lipid-binding serum glycoproteins and plays a significant role in the body’s defense against Gram-negative bacterial infections .
BPI was first identified by Jerrold Weiss and Peter Elsbach at New York University Medical School . The protein is primarily found in the granules of neutrophils, a type of white blood cell, but it is also present in other tissues, including the epithelial lining of mucous membranes . The structure of BPI is characterized by its strong affinity for lipopolysaccharides (LPS), which are components of the outer membrane of Gram-negative bacteria .
BPI exhibits potent bactericidal activity against Gram-negative bacteria. It functions by binding to the lipid A moiety of LPS, neutralizing the endotoxin’s ability to trigger an immune response . This binding not only kills the bacteria but also prevents the activation of the immune system by LPS, thereby reducing inflammation and potential tissue damage .
The protein’s N-terminal region is responsible for its bactericidal activity, while the C-terminal region is involved in binding to LPS . BPI’s ability to neutralize LPS makes it a critical factor in controlling infections caused by Gram-negative bacteria, such as Escherichia coli and Pseudomonas aeruginosa .
Given its potent antibacterial properties, BPI has been explored for various clinical applications. One notable development is the recombinant 21 kDa portion of the BPI molecule, known as rBPI21 or opebecan (NEUPREX), developed by Xoma Ltd . Clinical trials have shown that rBPI21 can reduce mortality in cases of Gram-negative bacterial-induced sepsis . Additionally, studies have demonstrated BPI’s effectiveness against Gram-positive bacteria and even protozoan infections, such as Toxoplasma gondii .
Research has also investigated the use of BPI in treating endotoxic shock. For instance, the N-terminal portion of murine BPI fused to Halobacterium sp. NRC-1 GvpC protein was tested using a murine model of endotoxic shock. The treatment resulted in increased survival and reduced inflammation symptoms .