CTSA Seminar
Novel functions of platelets in disease

8/9/15
Siddhartha Mitra

Platelets originate from megakaryocytes, through a budding process.

They were thought to be responsible primarily for clot formation, though now scientists feel they also take part in the immune response.

There are around 150,000 – 400,000 platelets per microliter, and 3 times that in mice. Average lifespan is 3-5 days. They are anucleate, and hence do not carry any transcriptional machinery.

However, they do appear to carry the splicing machinery for processing pre-mRNA’s, and also they carry the translational machinery for making proteins.

Certain pre-mRNA’s and microRNA’s are transported out of the megakaryocyte nucleus and into the platelets. Pre-mRNA presence is confirmed by the presence of intronic sequences present in RNA from platelets.

Thrombin induces increase in presence of Bcl-3 protein, via the mTOR pathway.

Mice with mTOR KO in megakaryocytes die quickly after abnormal sepsis induction through cecal ligation and puncture (CLP). These mice can be rescued by infusion of WT platelets.

Bcl-3 was earlier thought to essentially be a transcription factor. However, since platelets are anucleate, Bcl-3 must have other purposes. Possibly interaction with other kinases during fibrinogen formation, and also in actin filament formation during clotting.

Platelets shed IL-1beta protein carrying microparticles in response to dengue infection. They also interact with the inflammosome during this process. Possibly this reaction is also true for other ssRNA flaviviruses or other pathogens.

There is increased expression of IFITM3, which is induced by IFNgamma during viral infection. Dengue itself is also found in platelets. Not clear why the proteins get released, and why dengue is in platelets.

References:

http://www.bloodjournal.org/content/126/3/286?sso-checked=true