Lipid A

Lipid A is a lipidcomponent of an endotoxinheld responsible for toxicityof Gram-negativebacteria. However, sensing of lipid A by the human immune system may also be critical for the onset of immune responses to Gram-negative infection, and for the subsequent successful fight against the infection. Lipid A is located at one end of the lipopolysaccharide (LPS, also called endotoxin) molecule, and anchors the LPS to the outer membrane of a Gram-negativebacteria. Many of the immune activating abilities of LPS can be contributed to the lipid A unit. It is a very potent stimulant of the immune system, activating cells (for example, monocytesor macrophages) at picogramper milliliter quantities. When present in the body at high concentrations during a Gram-negative bacterial infection, it may cause shock and death by an "out of control" excessive immune reaction.

Chemical composition: Lipid A consists of two glucosamine(carbohydrate/sugar) units with attached unusual acyl chains ("fatty acids"), normally containing one phosphategroup on each carbohydrate. The optimal immune activating lipid A structure is believed to contain 6 acyl chains. The length of the carbon chains usually varies between C10 and C16, with some exceptions. E. coli lipid A, as an example, typically has five C14 and one C12.

Lipid A with a reduced number of acyl chains (for example; four) can serve as an inhibitorof immune activation induced by Gram-negative bacteria, and synthetic versions of these inhibitors are in clinical trials for the prevention of harmful effects caused by Gram-negative bacterial infections. On the other hand, modified versions of lipid A can be used as components of vaccines(adjuvants) to improve their effect.

Lipid A (and LPS) is believed to activate cells via Toll-like receptor 4 (TLR4), MD-2 and CD14 on the cell surface.

References

• Raetz and Whitfield; Annu Rev Biochem 2002; 71: 635-700 Raetz and Whitfield; Annu Rev Biochem 2002; 71: 635-700.

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It uses material from the http://en.wikipedia.org/wiki/Lipid+A Wikipedia article Lipid A.