THE little plate-shaped fragments that pack our blood seem to do much more than just help with clotting. Not only do they play an unexpected role in a host of diseases, they also fight infection and promote healing. Targeting these fragments may stop cancer from spreading, alleviate arthritis and open up new opportunities for treating diseases such as lupus and multiple sclerosis.
Platelets are well known for their role in preventing bleeding: once activated (pictured, on either side of a white blood cell), they clump together to form clots. People with too few platelets are at risk of serious bleeding if injured, while too many platelets can cause clots to form in the wrong place, triggering strokes, heart attacks or deep-vein thrombosis.
Now a slew of recent studies suggest that platelets may have many more strings to their bow. For example, at the Universit茅 Laval in Qu茅bec city, Canada, and his colleagues have found that platelets can enhance inflammation in a mouse model of arthritis by making blood vessels in the joints more 鈥渓eaky鈥�. A separate team has discovered that platelets work in cahoots with tumour cells to promote spreading, or metastasis.
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鈥淧latelets can enhance inflammation in arthritis by making blood vessels in the joints more leaky鈥�
Platelets鈥� hidden functions aren鈥檛 all bad, though. They also seem to produce the equivalent of human antibiotics: antimicrobial peptides that may be a vital first line of defence against invading micro-organisms. And another recent study found that platelets help direct bacteria to the spleen, enabling a full-blown immune response to be triggered (快猫短视频, 5 November 2011, p 19).
鈥淯ntil very recently we thought that platelets were just small cellular fragments that clump when there is bleeding,鈥� says Boilard. 鈥淏ut they are smarter than we thought.鈥�
Evidence that platelets may have other roles has been building for some time, although it has not been widely appreciated until very recently. In the 1990s, researchers started investigating the role of platelets in promoting wound repair after the discovery that bone grafts were more successful if their blood supply contained high concentrations of growth factors. It turned out that the source of these growth factors was platelets. Since then, doctors have started using a gel produced from patients鈥� own blood called platelet rich plasma (PRP) to boost the success of skin and bone grafts, as have some athletes to promote faster wound healing.
It soon became clear that the infection rate in recipients of this plasma also dropped, leading to the discovery of an antimicrobial substance called beta-defensin 2. To investigate further, at Aachen University in Germany and his colleagues used antibodies to tag beta-defensin 2, and then visualised it using an electron microscope. This enabled them to discover its source: tiny packages within platelets. They also showed that when released, beta-defensin 2 sticks to the surface of bacteria including E. coli, causing them to leak fluid and die (Platelets, ).
鈥淲e were surprised,鈥� says Pufe, who is now investigating whether PRP can reduce the infection rate following open bone fractures. 鈥淢ost people think the main role of platelets is blood clotting, and maybe a small role in tissue repair, not that they have antimicrobial potential.鈥�
Meanwhile, other researchers have been investigating platelets鈥� role in maintaining the semi-permeable lining of blood vessels, which allows fluid, nutrients and ions to pass to and from tissues. Recent research has hinted that they release chemicals to maintain the junctions between cells lining the vessels.
Inflammatory diseases like arthritis often result in the leakage of fluid from blood vessels, so Boilard鈥檚 team decided to investigate what platelets were doing in a mouse model of the condition. To their surprise, they found that platelets were causing gaps to form in the blood vessel walls through the release of serotonin, a chemical more often associated with influencing mood in the brain. Depleting platelet numbers reduced symptoms of arthritis, as did stopping them from storing serotonin using common antidepressants called selective serotonin reuptake inhibitors (Blood, ).
Just why platelets would contribute to arthritis remains a mystery for now, although it is possible that opening up the blood vessels is a useful step in normal wound healing, but something happens in arthritis that means the inflammatory signal doesn鈥檛 get switched off.
鈥淧latelets are little bags of goodies for promoting wound healing, and that can often promote other things as well,鈥� says of the David H. Koch Institute for Integrative Cancer Research at MIT.
Cancer is also often described as a wound that doesn鈥檛 heal, and Hynes has evidence that tumour cells are capitalising on a pathway involved in wound healing to help them spread around the body.
鈥淲hen platelet-activated pathways were blocked, cancer no longer spread around the body鈥�
High platelet counts have long been associated with poorer cancer survival, but no one understood why. Hynes and his colleagues have discovered that platelets bind to cancer cells and initiate chemical conversations that make the cancer cells more invasive as a result. When either these signalling pathways or the platelet receptors involved were blocked, metastasis didn鈥檛 take place (Cancer Cell, ).
The discovery raises the prospect of targeting this interaction to prevent metastasis, perhaps by using drugs like the clot-busting heparin, which interferes with platelet adhesion and activation. 鈥淭he question is whether blocking this process will do any good, because by the time a patient presents with cancer these steps have probably already happened,鈥� says Hynes.
A better understanding of platelets could lead to new therapies for a host of diseases. As well as arthritis, Boilard says there is evidence they may be implicated in lupus and multiple sclerosis.
However, of Louisiana State University in Shreveport warns their multi-functional role means that simply depleting platelets would be unfeasible and potentially dangerous. 鈥淏ut if you can find the underlying mechanism of how the platelets are contributing to disease, I think that will really help move disease treatment forward,鈥� she says.
