Neutrophils- the friend turned foe during heart attack

Just as we don’t care much about the guy running around with a bow and arrow in the Avengers (what was his name again?), platelets are also one of the most underappreciated characters of the human blood cell lore. Platelets are pivotal for orchestrating the process of sealing wounds from foreign invaders (clotting). However, excessive production of platelets can make your heart walk the plank as if may give rise to heart diseases. And in the grand scheme of giving your heart a hard time, platelets have a co-conspirator—a member of our prestigious immune system club – who was supposedly created to protect your body in the first place.

Platelets are produced and matured in the bone marrow, just like its other myeloid cousins. So far scientists have established that platelets are created by megakaryocytes, which are large multi-lobular cells that undergo fragmentation to form platelets. Unlike the other cells that traverse from bone marrow interstitial space (where blood cells, including megakaryocytes, are produced) into the blood vessels, megakaryocytes are too big to squeeze through the vessels completely. Instead, megakaryocytes lose their sphericity and funnel small overhangs of themselves into the vasculature. These overhangs are called pro-platelets because they eventually transform into mature thrombocytes. And how exactly does that happen? The blood in the vessels, owing to its high velocity, hits the pro-platelets like a truck and sort of drags them off along with it, breaking them at their point of attachment to the megakaryocyte. You might be wondering if the flow of blood alone can do this, what about the plethora of other cells that are also created in the bone marrow and pass through it daily?

It turns out there great point to this question. Petzold and colleagues have now discovered interactions between neutrophils and megakaryocytes in the bone marrow. Unlike blood flow, the neutrophils were not hitting the pro-platelets with sheer force to break them off but were instead doing something really outlandish. They were grabbing to the sites of pro-platelet attachment and were sort of biting it off, something the scientists liked to call neutrophil “plucking”. They used an imaging technique called intravital multiphoton microscopy, which can be used to see the interaction of cells in live tissue. Additionally, the fewer irregularly shaped megakaryocytes interacted more with neutrophils compared to abundant megakaryocytes with a conserved, spherical shape. This kind of makes sense since megakaryocytes must lose their perfectly spherical shape to squeeze into the vessels and contribute to platelet production in the first place.  

The researchers depleted neutrophils and saw that the platelet count in the neutropenic mice nosedived. To make sure that it was also the same the other way around when they restored the neutrophils again, the platelet count went back to normal! This confirmed the neutrophil-platelet interaction.

Now, the story doesn’t end here. The scientists tried to dig deeper. They wanted to figure out what were the baits that were luring the neutrophils to the site and insinuating them into performing the act of plucking.

After a lot of trial and error, they were able to make two solid conclusions:

  1. The interaction involved the chemokine receptor CXCR4 present on neutrophils and its ligand present conveniently on the surface of megakaryocytes. 
  2. The megakaryocyte-neutrophil physical contact triggers the release of reactive oxygen species in the neutrophils and simultaneously activates certain pathways in the megakaryocyte allowing the plucking and release of platelets.

Their experiments proved that neutrophil-driven platelet production occurs normally in our bodies, and it might be one of the several ways platelet homeostasis is maintained. But the researchers noticed that the neutrophil-platelet partnership caused some complications in the mice models. They saw that after a heart attack, for unknown reasons, platelet production led by neutrophils was speeding up abnormally. This led to the release of exacerbated amounts of immature platelets into the blood. Unlike mature platelets, immature platelets are highly unstable and can lead to erratic, spontaneous, unnecessary clots. Driving blood full of immature platelets right into the heart would be like nuking the heart right after it had already experienced an earthquake of magnitude 10!

Although an unfortunate 17.9 million lives are taken away by heart diseases globally every year, we can see some light at the end of the tunnel. Targeting neutrophil-driven platelet production to curb the chances of heart attack occurrence and recurrence may sound like a very niche approach since there is a myriad of other major reasons why heart attacks manifest. But regardless, it just might be another good step toward understanding what slowly strangles your heart, eventually choking it to death, and what can be done to help it avoid such an ill-fated ending.

Source:

Petzold T, Zhang Z, Ballesteros I, Saleh I, Polzin A, Thienel M, Liu L, Ul Ain Q, Ehreiser V, Weber C, Kilani B, Mertsch P, Götschke J, Cremer S, Fu W, Lorenz M, Ishikawa-Ankerhold H, Raatz E, El-Nemr S, Görlach A, Marhuenda E, Stark K, Pircher J, Stegner D, Gieger C, Schmidt-Supprian M, Gaertner F, Almendros I, Kelm M, Schulz C, Hidalgo A, Massberg S. Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. 2022 Dec 13;55(12):2285-2299.e7. doi: 10.1016/j.immuni.2022.10.001.

Article author: Lalit Anand. Lalit is a Biotechnology major at the Vellore Institute of Technology. He loves reading about the immune system and its peculiar interactions with other bodily systems.

Want your article featured in Antibuddies blog? Contact editor-in-chief- Dr. Sutonuka Bhar at antibuddies1@gmail.com.

Share this article in twitter by clicking below:

Check out Antibuddies’ blog post “Neutrophils- the friend turned foe during heart attack”


Posted

in

by

Comments

One response to “Neutrophils- the friend turned foe during heart attack”

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: