Platelets: a massive protein factory in our body

Platelets are the unsung heroes in our blood. 

Each day, in every human, approximately 1 × 10¹¹ (100 billion) platelets are produced. The process starts in the bone marrow with a megakaryocyte. The platelet's parent cell is the largest cell in the bone marrow (1): 

•  Megakaryocyte 50 - 100 micrometer (μm) diameter
•  White blood cell ~15 μm diameter
• Red blood cell ~7 μm diameter

In the image above, the two types of cells seen are the purplish platelets and the pinkish-red red blood cells, neither of which has a nucleus. The reason that the platelets stain purple is because they contain large quantities of ribonucleic acid (RNA) which binds the basic blue stain in hematoxylin and eosin (H&E) staining. 

To generate platelets, the megakaryocyte separates its cytoplasm down into 10 - 20 elongated pieces (proplatelets). It pushes those cytoplasm fragments through the blood vessel walls in the bone marrow, as if it were pushing its cytoplasm through a pasta-making machine. Each of those pro-platelets further subdivides into 2,000 - 5,000 platelets. On the average, one megakaryocyte generates 10,000 platelets (1)!

None of those break-off fragments of the megakaryocyte have a nucleus. As its final act, the denuded megakaryocyte cell extrudes its nucleus out of its stripped cell remnant. The nucleus is then eaten up by macrophages.

Platelets are one of our first responders in our blood. Any time we cut ourselves or are exposed to a foreign entity, the platelets are there to save the day.

Here's what happens: When stimulated with proteins that are not normally circulating in the blood (like collagen from the injured tissue), the platelets start releasing activating proteins from their small cytoplasmic granule packages: 

•  Coagulation factors
• inflammatory proteins
• Immune system activators

Within seconds, platelets have attracted others and joined together to form a platelet plug. The activated platelets recruit other cells into the fray to enable healing, including white blood cells such as neutrophils and macrophages (3). The latter are scavenger cells, eating up bacteria and cell debris. 

2a. What is the role of platelet-produced growth factors?

Most importantly, activated platelets secrete growth factors into the surrounding milieu.

Platelets are a biological factory for many proteins. One group that is particularly important is the growth factors protein group. These include (3): 

• The platelet-derived growth factor (PDGF)
• The transforming growth factor beta-1 and -2 (TGF-β1 and 2),
• bone morphogenetic proteins (BMPs),
• Vascular endothelial growth factor (VEGF)
• basic fibroblast growth factor (bFGF)
• hepatocyte growth factor (HGF)
• epidermal growth factor (EGF),
• insulin-like growth factor-1 (IGF-1)

We don't have to memorize this list. I just note the different growth factors to highlight the diversity of proteins that platelets generate when stimulated. As soon as they are activated, the platelet granules release their protein cargo into the blood. These critical growth factors induce proliferation of fibroblasts as well as endothelial cells at sites of injury (3). This allows tissues to start the repair process. 

Platelets have a multitude of ways to generate the large mass of proteins within their granules. First, they inherit the proteins from their parent cell, the megakaryocyte, which has already prepared the granule packages. Second, they absorb proteins from the extracellular fluids by sucking up floating pieces of protein. Finally, platelets can manufacture proteins using mRNA that has already been stowed away in the platelet cytoplasm (3, 4).

Finding cells that don't have DNA - that is, anucleate platelets - synthesizing their own protein was an eye-opener in the 1960s. And researchers consistently demonstrated this finding in study after study over the next 40 years.

What is even more interesting is that platelets are not one-size-fits-all response factories. They synthesize different proteins depending on the type of stimulation that they encounter. They demonstrate plasticity in their response to the environment.

For interactions with bacteria, they produce one set of proteins; for interactions with extracellular proteins - like collagen, they produce an alternate set. Research suggests that platelets have the capacity to produce 5000 different types of proteins (3, 4).

Finally, because platelets have the complete protein synthetic machinery in their cytoplasm factories, they can stay quiescent until they are activated by the different signals (4, 8).

Keep in mind that even quiescent - non-activated - platelets are quietly producing proteins to make up for any losses. Thus, platelets sitting in the blood bank in storage are translating their mRNA into proteins. This is pretty nifty for a cell whose lifespan is only 10 days (4).

There are a number of platelet-associated inherited diseases that lead to problems with either packaging or secreting growth factors. For example, patients afflicted with the Gray Platelet Syndrome don't have alpha-granules in their platelets. Alternately, their small cellular factories may have granules but those are like empty boxes within the cytoplasm.This means they lack the ability to secrete clotting factors or growth factors. 

Since the alpha granules' growth factor proteins have many acidic groups and stain purple under the microscope with basic stains like Hematoxylin, platelets in patients with Gray Platelet Syndrome appear pale or gray. Patients with this disease have problems with forming clots after injuries and experience mild to moderate bleeing (8).

4a. Platelets, growth factors, and healing

Interestingly, there are also genetic mutations that increase the expression of transforming growth factor beta receptor III (TGF-β R type III) protein in platelets. This causes havoc as those platelets cannot produce normal alpha-granules, leading to problems in the generation of platelets. Families with affected members have lower than normal numbers of platelets and many have lifelong spontaneous bruising, nosebleeds, or prolonged blood loss from injuries (9).

Clearly, platelets' function and vitality are intricately related to normal growth factor functioning. In this vein, platelet-generated alpha-granule- protein-enriched fluid preparations (produced from thrombin-activated platelets) are used in wound healing for chronic wounds (8).