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Endotoxins (not to be confused with exotoxin) are toxins[1] associated with certain Gramnegative bacteria.

An "endotoxin" is a toxin that is a structural molecule of the bacteria that is recognized by the immune system.

Lipopolysaccharide and other endotoxins


[edit] Gram negative

Structure of a lipopolysaccharide The prototypical examples of endotoxin are lipopolysaccharide (LPS) or lipooligosaccharide (LOS), found in the outer membrane of various Gram-negative bacteria and are an important component of their ability to cause disease.[2] The term LPS is often used interchangeably 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" came from the discovery that portions of Gram -negative bacteria themselves can cause toxicity, hence the name endotoxin. Studies of endotoxin over the next 50 years revealed that the effects of "endotoxin" were, in fact, due to lipopolysaccharide. LPS consists 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 amon gst different bacteria. Endotoxins are approximately 10 k in size but can form large aggregates Da up to 1000 kDa. Humans are able to produce antibodies against 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 hasbeen shown to produce fever, a decrease in 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 meningitidis, the pathogens that causes meningococcal disease, including meningococcemia, WaterhouseFriderichsen syndrome and meningitis.

Mechani
In humans, LPS binds t the li id binding protein (LBP) in the serum whi h transfers it to CD14 on the cell membrane, which in turn transfers it to another non-anchored protein, MD2, which associates with Toll-li e receptor-4 (TLR4). CD14 and TLR4 are present in several immune system cells (including macrophages and dendritic cells), triggering the signaling cascade for macrophage/endothelial cells to secrete pro-inflammatorycytokines and Nitric oxide that lead to "endotoxic shock". Other than TLR4, components of gram negative cell wall may also activate other pathways which may contribute to the overall endotoxic effect.

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