Monday, November 21, 2011

Inhibition of just one molecule makes treatment of both tumours and wounds possible

A newly discovered cellular mechanism provides clues to both how our body tries to fight off tumours, as well as killing micro-organisms in wounds. Both processes involve the immune system, which's first line of defence consists of a group of cells called neutrophils. These cells are first to be on site, and the mechanism by which they are activated has recently been discovered by a group of scientists from the University of Wisconsin-Madison. A tumour, or a wound, generates large amounts of hydrogen peroxide, which causes neutrophil activation, which basically jump-starts the immune response. Discovering how this mechanism can be utilized could be beneficial to developing new methods to improve wound healing and tumour killing.

It was found that hydrogen peroxide modifies a molecule called lyn on neutrophils. This results in intracellular signalling that consequently results in activation. While this constitutes a mechanism needed to provide basic support in the immune response to fight off infections, it is not always beneficial for the body. Because wounds produce such large amounts of hydrogen peroxide, the corresponding neutrophil response can actually be harmful. An extreme activation of the immune system as result of the high hydrogen peroxide production can result in chronic inflammation. This means the problem is not being resolved, but instead the immune system is kept in active state.

Neutrophil response to tumours can be equally harmful. Malicious cells can sometimes use the inflammatory response by the immune system for their own benefit. Instead of killing the cancer cells, the body's response induces extra growth, and aids in the spread of the tumour throughout the body. A previous study already discovered that cancer cells can spread by harnessing signals coming from the blood.

The researchers discovered that lyn is responsible for the neutrophil response at wounds and tumours. Blocking this particular molecule resulted in a decrease in neutrophil activation. However, the scientists believe that the immune system fights off infections by means of other cellular pathways, which means the inhibition of lyn would selectively inhibit the damaging neutrophil response in the case of excess hydrogen peroxide production. In addition, other immune cells are still able to kill malicious tumour cells, even though the neutrophils have been knocked out. New treatments based on this mechanism could prevent chronic inflammation in wounds, and prevent tumours from hijacking the immune system to promote their growth.

Classical forms of immune system activation include so-called antigen-presenting cells. These scavengers circulate throughout the body and engulf all foreign particles. This includes bacteria, viruses, but also dead material that does not belong in the body. After processing, their discovery is presented to highly specialized white blood cells, who become activated with high specificity to kill the intruders. B cells produce antibodies; circulating molecules that attach to foreign objects, rendering them dysfunctional, and marking them for degradation by other immune cells. In contrast, T cells become so-called 'killer cells' that are able to destroy infected cells by production of cytotoxic factors.

1 comment:

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