Endotoxin
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Endotoxins are potentially toxic, natural compounds found inside pathogens, like bacteria. Classically "endotoxin" is a toxin which unlike "exotoxin"s is not secreted in soluble form by live bacteria, but is a structural component in the bacteria which is released mainly when bacteria are lysed.
The prototype example of an endotoxin is part of the outer membrane of the cell enveloppe of Gram-negative bacteria. Its main active ingredient is the lipopolysaccharide (LPS) or lipo-oligo-saccharide (LOS) complex associated with the outer membrane of Gram-negative bacteria. The term LPS is often used exchangeably with endotoxin, owing to its historical discovery. In the 1800s it became understood that bacteria could secrete toxins into their environment, which became broadly known as "exotoxin". The term endotoxin comes from the discovery that portions of Gram-negative bacteria itself can cause toxicity, hence the name endotoxin. Studies of endotoxin over the next 50 years revealed that the main molecule responsible for the effects of "endotoxin" was in fact lipopolysaccharide. However thare are endotoxins other than LPS. For example delta endotoxin of Bacillus thuringiensis makes crystal like inclusion bodies next to the endospore inside the bacteria. It is toxic to larvae of insects feeding on plants, but is harmless to humans( as we do not possess the enzymes and receptors necessary for its processing followed by toxicity).
LPS consist of a polysaccharide ("sugar") chain and a lipid moiety, known as lipid A, which is responsible for the toxic effects. The polysaccharide chain is highly variable amongst different bacteria. Humans are able to produce antibodies to endotoxins after exposure, but these are generally directed at the polysaccharide chain, and do not protect against a wide variety of endotoxins. Injection of a small amount of endotoxin in human volunteers produced fever, a lowering of the blood pressure, and activation of inflammation and coagulation. Endotoxins are in large part responsible for the dramatic clinical manifestations of infections with pathogenic Gram-negative bacteria, such as Neisseria meningitides (that causes fulminant meningitis).
In our body LPS binds to the lipid binding protein (LBP) in the serum which transfers it to CD14 on cell membrane, which in turn transfers it to another non-anchored protein MD2 which associates with Toll-like receptor-4. CD14 and TLR4 is present in several immune system cells (including macrophages and dendritic cells), triggering the signalling cascade for macrophage/endothelial cells to secrete pro-inflammatory cytokines and Nitric oxide which lead to the "endotoxic shock". Other than TLR4, components of gram negative cell wall may also activate other pathways which may contribute to the over all endotoxic effect.
Endotoxins are frequent contaminants in plasmid DNA prepared from bacteria, and must be removed from the DNA to avoid unwanted inflammatory responses prior to in vivo applications such as gene therapy.
In pharmaceutical production, it is necessary to remove all traces of endotoxin from drug product containers, as even small amounts of endotoxin will cause illness in humans (but not disease). A depyrogenation oven is used for this purpose. Temperatures of approximately 400 degrees celsius are required to break down this substance.
A very sensitive assay for detecting presence of endotoxin is Limulus (horse shoe crab) lysate assay. Very low levels of LPS can cause coagulation of the limulus lysate due to a powerful amplication through an enzymatic cascade.
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Template:Bacteria-stubde:Endotoxin ja:内毒素 nl:Endotoxine pt:Endotoxina