Neutrophils rule!

Several people have asked me recently, what are neutrophils?  That is a great question, and I can't wait to show you how amazing neutrophils are.  I "phoned a friend" to help me with this post because she is a talented neutrophil enthusiast.  R is one of my best friends from graduate school and has been studying neutrophils (among other things) for several years.  I asked her to write a list of things my audience should know about neutrophils.  Here it is, complete with some truly amazing movies that show neutrophils in action.  (If you only have time to watch one of the movies, let it be the first one, "neutrophil chasing bacterium".  It will blow your mind!  This happens in YOUR body!)  So sit back, open your mind, and release your inner nerd!  Enjoy!

Neutrophils Fun Facts (in no particular order):

1) They’re the first line of defense against bacteria--when bacteria arrive someplace in your body that they’re not meant to be, like a cut in the skin or an abscess in the mouth, a variety of signals are released that make neutrophils migrate to that site, where they do their best to eradicate the infection.  Below is a movie of a crawling neutrophil chasing a bacterium.

2) They’re what pus is made of! The white goo that we call “pus” is actually a big glob of white blood cells, most of which are neutrophils, that have come there to fight infection. Also, one of their main enzymes contains iron, which is why pus is often a little greenish.

3) They live for less than a day--the life cycle of a neutrophil is estimated to be 10-18 hours, although recently a controversial paper suggested that it could be longer, more like 5 days. During their lifespan, they are born and mature in the bone marrow, and then circulate throughout the bloodstream, waiting to detect signals of an infection that requires their presence.

4) Neutrophils can totally change their shape as the situation requires. In your blood, they are completely round and can roll along the sides of the blood vessels. To squeeze between cells, they can deform themselves and squeeze through a gap roughly 1/10 their size. Once in the tissues, they flatten out and develop a leading migrating edge--imagine a bloodhound with its nose to the ground, scenting a trail; this is how they move when they’re trying to follow a chemoattractant path to get to an infection.
Below is a movie showing how neutrophils roll along the walls of a vein and squeeze through the wall when needed.

5) If they don’t find any bacteria to fight, they undergo programmed self-death (apoptosis), and then mark themselves with a molecular flag for other cells (macrophages) to clear them away.

6) They are superpowered killing machines. Neutrophils’ job in the body is to kill invading pathogens, and they can do this in a variety of ways:

Phagocytosis- Neutrophils can eat bacteria, and once they’re inside, kill them via production of extremely toxic free radicals (aka the things that antioxidants protect you from!). Amazingly, the neutrophils can kill the bacteria this way without damaging themselves.

Degranulation- not all neutrophils responding to an infection will meet up with a bacteria to kill. If a neutrophil senses that its killing abilities are needed but doesn’t know exactly where, it can release all of its toxic weapons into the environment near the infection. This includes a number of cool things:

Antimicrobial peptides- these are compounds that kill all kinds of bacteria, often by punching a hole in their membrane or starving them of necessary metals.

Digestive enzymes- neutrophils manage to store very powerful enzymes in granules without hurting themselves, but once they are secreted they go to town digesting everything in sight.

Reactive oxygen species- you know how you can put hydrogen peroxide on a scrape to disinfect it? Well, neutrophils not only produce compounds like hydrogen peroxide, they make an enzyme (myeloperoxidase) that makes these compounds even more toxic. Bad news for bacteria.

DNA nets- This is a supercool finding of the last ten years. Neutrophils can actually excrete all of their DNA, which is sticky and acts as a “net” to trap bacteria, keeping them in place so they can’t escape the other killing mechanisms.

7) Neutrophils are the most abundant immune cell in the blood-- they make up about 50-70% of your circulating white blood cells.

8) Because neutrophils are such powerful killing machines and can release their molecular weapons indiscriminately, it’s very important that we regulate their behavior and make sure they’re only deployed when and where they’re needed. This is accomplished by a step-by-step cascade of signals--picture the game mousetrap, where the neutrophil starts in the bloodstream and ends up killing bacteria in the tissues.

9)  (This one was added by Heather, because the relationship between neutrophils and neutropenia is a common question that I get asked) The importance of neutrophils in fighting infections is why it is a serious health risk to have too few neutrophils.  Having too few neutrophils (below 1000 in a blood sample) is called neutropenia.  Neutropenia can be caused by a number of medical issues, including chemotherapy.  There is one treatment that can help increase neutrophil levels, and that is a drug called G-CSF (granulocyte-colony stimulating factor).  The formulation I have been given is called Neulasta, but there are others as you can see if you follow the link.  This formulation in Neulasta is auto-regulated, meaning it starts to work once the levels of white blood cells are low.  This is why my white blood cell counts experience a lag--I'm neutropenic a week after receiving Neulasta, but then the Neulasta kicks in and fixes me right up.  Once my white blood cells increase, they get rid of the Neulasta and my body takes care of itself again.  This is important because you wouldn't want Neulasta, or any formulation of G-CSF, working all the time, because having too many white blood cells is a different kind of problem.

Please post questions in the comments section. R and I will either answer them ourselves or direct you to a resource that can.  We hope you enjoyed learning a bit of biology today!  Also, for those of you who pay attention to every detail (ahem sisters), no I did not write this post on my sickest day.  I pre-wrote it and set it to post automatically for you, my dear readers.  All my love!