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The Tick and the Blood Pool

March 15, 2011

I don’t like spiders.

I don’t kill them because I appreciate they keep the flies down etc. etc. but I really don’t like them.  Actually, it isn’t them per se, but their legs…

So why I started looking at another paper on eight-legged critters I have no idea!  But it’s a very interesting paper, and at least this one deals with ticks rather than spiders – a slight improvement in my book.

Ixodid ticks (also known as ‘hard ticks’) are found across the world and are vectors of blood-borne diseases including Lyme disease, Rocky Mountain spotted fever and babesiosis to name a few.  (A more comprehensive list of tick-borne diseases .)  Ticks have to feed on blood to live and when they feed it is for days at a time rather than for the few seconds a mosquito feeds.  You will know yourself that if you cut yourself (superficially!) you normally stop bleeding pretty quickly – your blood coagulates and forms a clot.  For the tick to feed for days it must be producing something that either stops that clot from forming or somehow allows it to bypass the clot.  In fact, ticks create ‘blood pools’ beneath the host’s skin that consist of unclotted blood and exudates.  Previous work has shown that ticks release a variety of products into the host when they feed and the authors of this paper have previously published work identifying one of these bio-molecules, called longistatin.  In this paper the group of researchers looked at longistatin in more detail

First, the researchers created ticks that couldn’t express longistatin.  They found that ticks that can’t produce longistatin can’t create a blood pool in a host and so can’t feed properly.  You might not want to look at the cool figure below if you’re squeamish…but it shows that the control ticks fed normally, forming a blood pool and increasing in size, whereas the ones that couldn’t produce longistatin didn’t form the blood pool and didn’t feed successfully.

If a tick can't produce longistatin what happens? This is part of a figure from the paper (doi:10.1371/journal.ppat.1001312.g002). The dsmalE ticks are the controls and the dslongistatin ticks the ones that can't produce longsitatin. A and B show that the ticks that can't produce longistatin failed to feed properly and C shows their failure to produce a prominent blood pool.

This finding led the researchers to look at why that should be the case.

Blood clot formation is a complex process that I never quite got my head around as an undergrad despite staring at diagrams similar to the one below for hours (admittedly the night before the exam).  I pretty much get it now (I think) but if anyone out there would like to correct me – feel free!

I’m going to focus on the aspects of the clotting cascade relevant to this paper but for more information this page is a reasonable place to start.

The Clotting Cascade. (Taken from: DOI 10.1371/journal.ppat.1001312)

 

For the purpose of this paper we need to concentrate on the bottom of the diagram.  After damage to a blood vessel (caused by, for example, a tick bite) platelets become activated and collect around the injured area forming a ‘platelet plug’.  Fibrinogen is cleaved to form fibrin and these fibrin strands bind to the platelets and strengthen the plug.  Factor XIII then acts to stabilise the clot further.

The researchers found that longistatin degrades fibrinogen and by doing this delays clot formation.  Obviously longistatin is therefore a very useful product to have when you need to feed off a pool of blood.

Longistatin appears to be doubly useful as the researchers found that it activates plasminogen.  As shown in the diagram plasminogen is activated to plasmin.  Plasmin is one of the body’s methods of regulating blood clot formation and acts to cleave fibrin into fibrin degradation products, so breaking down the clot.

So not only does longistatin delay clot formation, when the clot does form it acts to destabilise it.

So why is this important?  Well clearly new knowledge is exciting itself without it having a further application but in this case there are several.  As I mentioned before, ixodid ticks are responsible for the spread of several blood-borne diseases.  The researchers suggest that longistatin could be a novel therapeutic target against ticks – if the ticks can’t feed for prolonged periods of time this could potentially mean a decreased risk of disease spread.  The researchers also suggest that as longistatin is an anticoagulant it, or products like it, could have a potential use in human diseases such as thrombosis (where a blood clot forms inside a blood vessel with potentially fatal effects.) 

Longistatin could turn out to be very useful…

 

Citations

Anisuzzaman, ., Islam, M., Alim, M., Miyoshi, T., Hatta, T., Yamaji, K., Matsumoto, Y., Fujisaki, K., & Tsuji, N. (2011). Longistatin, a Plasminogen Activator, Is Key to the Availability of Blood-Meals for Ixodid Ticks PLoS Pathogens, 7 (3) DOI: 10.1371/journal.ppat.1001312


Anisuzzaman, ., Islam, M., Miyoshi, T., Alim, M., Hatta, T., Yamaji, K., Matsumoto, Y., Fujisaki, K., & Tsuji, N. (2010). Longistatin, a novel EF-hand protein from the ixodid tick Haemaphysalis longicornis, is required for acquisition of host blood-meals☆ International Journal for Parasitology, 40 (6), 721-729 DOI: 10.1016/j.ijpara.2009.11.004

Klompen, H., (2005).  Ticks, the ixodida.  In: Marquardt WC, ed. Biology of Disease Vectors.  London: Elsevier Academic Press.  pp 197-212

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