Endotoxin

From Academic Kids

Endotoxin is part of the outer membrane of the cell wall of Gram-negative bacteria. It refers to the lipopolysaccharide (LPS) complex associated with the outer membrane of Gram-negative bacteria. LPS is also called 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 the actual molecule that produced the effects of "endotoxin" was in fact lipopolysaccharide.

Endotoxins consist of a polysaccharide ("sugar")chain and a lipid moiety, known as lipid A, which is reponsible 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).

LPS has been demonstrated to bind to Toll-like receptor-4 of several immune system cells (including macrophages and dendritic cells), triggering the signalling cascade for macrophage/endothelial cells to secrete pro-inflammatory cytokines. The binding to TLR-4 requires the presence of the serum factor Lipopolysaccharide Binding Protein (LBP).

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.

Template:Bacteria-stubde:Endotoxin nl:Endotoxine ja:内毒素

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