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Using NETs to ensnare bacteria

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The process of phagocytosis, by which neutrophil and macrophage white blood cells, among others, defend the body against pathogenic attack, is well known. Neutrophils form the main primary response, engulfing up to 25 pathogens, before undergoing programmed cell death, or apoptosis. The much larger macrophages then phagocytose the dead neutrophils and their contents, completing the inflammatory response.

Research has produced newer evidence of another, previously unknown, mechanism by which leucocytes deal with pathogens. In some circumstances, instead of phagocytosis, neutrophils release a combination of proteins and DNA from within the cell that act together to trap and inactivate bacteria. They are known as neutrophil extracellular traps (NETs).

The released DNA unravels into a web of fibres containing entrapped histones and proteases, which trap both Gram negative and Gram positive bacteria and kill them. One component of these NETs, the protein elastase, is capable of degrading bacterial virulence factor. It is thought that the formation of NETs is an active process unrelated to neutrophil apoptosis, since the NETs form within 10 minutes of pathogenic stimulation and do not contain other intracellular cytoplasmic proteins.

A study published recently in the journal Frontiers of Immunology has described similar extracellular traps produced by macrophages that have been found in particularly large numbers in obese mice, within rafts of dead fat cells surrounded by macrophages. It is thought that in this extracellular environment, the traps may feed a vicious circle of inflammation leading to the development of disease states, including cancer.

Of particular concern in overweight women is breast cancer, in which crown-like structures consisting of dead fat cells surrounded by macrophages have been observed. Further studies have suggested that the structures release inflammatory signals which increase the risk of breast cancer developing.

The team have developed a drug that appears to block trap formation, and it is hoped that this may form part of future treatment by suppressing inflammation within inflammatory environments in women who are obese, therefore preventing disease progression to the cancerous stage.

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From: Beyond pharmacy blog

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