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A new role for macrophages?

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I have just stumbled across an article, purely by typing the wrong thing into google. I put it down to fate! I found some fascinating research that I hope interests one or two of you as well as me!


It turns out that our immune system, specifically leukocytes, have a huge role in metabolic disease and are intrinsically linked with obesity. 


When we look at tissues under a microscope, there are normally some ‘other stuff’ that we can see as well as the tissue, including white blood cells.  It was always thought that these were transient and had been caught during the tissue biopsy, playing no significant role.  But when scientists have looked closer, these leukocytes are not there purely by chance.  Specific macrophages create a niche environment in certain tissues, with different lineages occupying different organs.  When these macrophages were wiped out, it appears that the same niche multiplied and restored normal levels, showing that this was not just coincidence. 


But why are these macrophages colonising normal tissue and healthy organs?  Is there a need for them there?


Now chemokines will be released in certain circumstances and allow macrophages to be directed to the site where they are needed, but these tissue specific macrophages seem to be present in non infected tissues.  Much research has now been conducted that is showing macrophages to have a non immunological function.  They seem to receive and act upon signals from damaged areas of the tissue and initiate repair by, for example, releasing initiation factors.


Pro-inflammatory mediators are released from macrophages when present in adipose (fat) tissue whereas anti-inflammatory mediators are released from those macrophages in lean tissue.  These both occur in white adipose tissue.  Brown adipose tissue has the unique characteristic of being able to be broken down, by oxidising fatty acids and producing heat to keep a person warm when acclimatising to cold temperatures.  The switch to allow brown adipose tissue to be broken down has now been found to go through macrophages.  This means that we have macrophages acting as a messenger in a cascade, signalling for the breakdown of both brown and white adipose tissue, aka fat!  Researchers have found that interleukin 4 increases the sensitivity of the macrophage to these signals and allows for increased levels of fat breakdown.


Now, this is important for pharmacists because it may offer a new therapeutic target for one of the fastest growing health problems around the world.  Not only is obesity dangerous alone, it also predisposes a person to an increased chance of other co-morbidities such as type 2 diabetes mellitus, hypertension, MI, stroke, the list goes on.  Is this already disregulated in obese patients?  Could this be exploited as a drug target?  Only time, and a lot more research, will tell but it looks exciting to me!

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