BPI is an antibacterial peptide, also known as bacteriolytic/permeability-inhibiting protein (BPI), which serves as a bactericidal and anti-inflammatory treatment for pathogens both in vitro and in vivo.
Background of BPI
BPI is an antibacterial peptide first isolated from humans by Froehlich et al. at the University of Washington School of Medicine in 1985. It is a glycoprotein composed of 153 amino acids with a molecular weight of 55 kDa. BPI is mainly present in neutrophils and can also be found in the blood. In addition, the presence of BPI can also be detected in organs and tissues such as the liver, lungs, and intestines of humans. The gene locus of BPI is 20q11.2-q12, which is a single copy gene.
The BPI can bind to the outer membrane lipid A (LPS) of most Gram negative bacteria and interact with acetylated LPS in the cell wall of Gram positive bacteria through its two C-terminus subunits, and destroy the bacterial cell membrane. BPI can also randomly activate its inherent bacterial toxin enzyme activity, enabling it to exhibit strong bactericidal activity in low concentrations of LPS. At the same time, the N-terminal of BPIalso has the function of neutralizing acetylated LPS, enabling BPI to fight against pathogens both in vivo and in vitro.
The Function of BPI
The main function of BPI is to provide bactericidal and anti-inflammatory treatment for pathogenic bacteria both in vitro and in vivo. The binding of BPI to bacterial LPS can damage its cell membrane and lead to its death. BPI has direct bactericidal activity against infected gram-negative bacteria such as Escherichia coli, Salmonella, etc. In addition, BPI also has the ability to neutralize acetylated LPS. Therefore, BPI plays an important role in killing and clearing pathogens.
BPI also plays an important role in immune monitoring and inflammatory response in the body. The expression level of BPI in neutrophils can reflect the degree of inflammation in the body, and an increase in BPI level is positively correlated with inflammation. In addition, it was found that BPI can directly promote the antigen presentation process on immune cells in the body, and can also serve as an antiviral peptide to inhibit virus growth to a certain extent.
BPI related signaling pathway
BPI is one of the various factors that play a role in infection and inflammatory response. The regulation of immune response in the body involves multiple signaling pathways, such as Toll like receptors (TLRs), cytokines and their receptors, and NF- κ Class B. The main signaling pathway of BPI is the MyD88 dependent TLR signaling pathway. In infection and inflammatory response, BPI can inhibit the activation of NFκB by interacting with TLRs to regulate the process of inflammatory response. In some cases, BPI can also eliminate cancer cells through a "apoptosis induction" mechanism similar to anticancer drugs that regulate immune responses.
Diseases related to BPI
BPI plays an important role in the development of endogenous immunity and immune diseases. The absence or abnormality of BPI can lead to susceptibility to infection in the human body, and even endogenous infections, such as sepsis. In certain immune disease patients, low levels of BPI, like other inflammatory processes, can lead to an increase in the body's inflammatory response.
BPI plays an important role in respiratory diseases such as pneumonia, tuberculosis, and influenza. Research has shown that BPIcan alleviate symptoms of acute pneumonia and improve lung function (such as increasing lung ventilation and improving lung oxygenation); For influenza pneumonia, the treatment of BPI can reduce virus input and load, prevent virus replication process, and alleviate inflammatory response, thereby effectively inhibiting the development of the disease.
The Application of BPI Protein in Medicine
BPI has been applied in various medical fields. In clinical practice, BPI has been used in the treatment of medical diseases, infectious diseases and tumors. Many studies have shown that BPI induced cell apoptosis has important application prospects in cancer treatment. At present, the clinical application of BPI is still expanding.
List of BPI related drugs under research
As a broad-spectrum antimicrobial peptide, the specific mechanism of action of BPI is constantly being studied and explored. Multiple drug research and clinical studies related to BPI are currently underway. For example, synthetic peptides of BPI can mimic BPI molecules to a certain extent, with higher activity and lower toxicity, and are expected to have more potential. Currently, BPI has some clinical applications and there is still great room for development in the future.
XENP717: XENP717 is a synthetic analogue of BPI protein with similar biological activity to BPI protein. The drug is being developed for the treatment of severe infections such as sepsis and septic shock.
BPI-1: BPI-1 is a recombinant BPI protein with strong bacterial killing effects. The drug is currently being studied for the treatment of respiratory infections and pneumonia.
LTX-109: LTX-109 is an artificially synthesized BPI protein analogue with broad-spectrum antibacterial activity. The drug is being studied for the treatment of various bacterial infections.
PMX205: PMX205 is a molecule with a BPI protein domain that can be used as a target for broad-spectrum antibacterial and anti-endotoxin activity. The drug is being studied for the treatment of sepsis and septic shock.
