Bactericidal permeability-increasing protein (BPI) is a 456-
residue
Residue may refer to:
Chemistry and biology
* An amino acid, within a peptide chain
* Crop residue, materials left after agricultural processes
* Pesticide residue, refers to the pesticides that may remain on or in food after they are applied ...
(~50k
Da)
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that is part of the
innate immune system
The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...
, coded for in the human by the ''BPI'' gene.
It belongs to the family of
lipid-binding serum glycoprotein
In molecular biology, the lipid-binding serum glycoproteins family, also known as the BPI/LBP/Plunc family or LBP/BPI/CETP family represents a Protein family, family which includes mammalian lipid-binding Serum (blood), serum glycoproteins and/or ...
s.
Distribution and function
BPI was initially identified in
neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...
s, but is found in other
tissues including the
epithelial
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
lining of
mucous membranes.
It is an endogenous antibiotic protein with potent killing activity against
Gram-negative bacteria. It binds to compounds called
lipopolysaccharide
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...
s produced by Gram-negative bacteria. Lipolysaccharides are potent activators of the
immune system
The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...
; however, BPI at certain concentrations can prevent this activation.
BPI was discovered by Jerrold Weiss and
Peter Elsbach at
New York University Medical School
NYU Grossman School of Medicine is a medical school of New York University, a private research university in New York City. It was founded in 1841 and is one of two medical schools of the university, with the other being the Long Island School of ...
.
rBPI21
Because lipopolysaccharides are potent
inflammatory agents, and the action of antibiotics can result in the release of these compounds, the binding capacity of BPI was explored as a possible means of reducing injury.
Xoma Ltd. developed a
recombinant 21kDa portion of the BPI molecule called rBPI
21, NEUPREX, or opebecan. In a trial, it was found to decrease the mortality of Gram-negative bacterial-induced sepsis. Studies suggest that its binding activity is not the means by which it mediates its protective effect. Studies show biological effects with
Gram-positive bacteria
In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall.
Gram-positive bact ...
and even in infection by the
protozoa
Protozoa (singular: protozoan or protozoon; alternative plural: protozoans) are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris. Histo ...
n, ''
Toxoplasma gondii
''Toxoplasma gondii'' () is an obligate intracellular parasitic protozoan (specifically an apicomplexan) that causes toxoplasmosis. Found worldwide, ''T. gondii'' is capable of infecting virtually all warm-blooded animals, but felids, such as d ...
''.
The N-terminal portion of murine BPI (199 amino acids) genetically fused to Halobacterium sp. NRC-1 GvpC protein was bound to the surface of gas vesicle nanoparticles (GVNPs) and tested for protective activity using a murine model of endotoxic shock. Depending on the time of delivery and exposure to lethal concentrations of lipopolysaccharide (LPS) and D-galactosamine, the treatment resulted in increased survival and reduced symptoms of inflammation, including inflammatory anemia, recruitment of neutrophils, liver apoptosis as well as increased pro-inflammatory serum cytokine levels. When administered via footpad and before LPS exposure, there was 100% survival of the experimental cohort.
References
External links
*
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