September 17, 2012 | 1
I’d like to tell you a secret. I am a superhero. I can devour my enemies whole, release my own chemical weapons and trap and kill my prey in nets spun from my own DNA. And I don’t even need to wear my pants on the outside.
I am a neutrophil, and several billion of me are made in your bone marrow every day.
Neutrophils are the most abundant white blood cell in the human body. They play a vital role in an ancient, rapid response called the innate immune system which is our first line of defense against disease-causing microbes. This system can mount a protective offense within minutes of the body being invaded, before the nature of the attack is known. This buys time for the body to produce a tailored response. The neutrophil is at the heart of the action, a killing machine that destroys unwanted intruders.
The neutrophil has many enemies. Perhaps you have a snot-filled toddler, a slobbery dog, or a propensity for paper cuts, but there will be something that exposes you to infection. Within minutes of infection invading your body the damaged tissue releases a chemical distress signal that attracts neutrophils out of the blood stream and activates them.
Activated neutrophils employ three key killing strategies. First, they can engulf and devour microbes. This process, called phagocytosis, was first described over one hundred years ago by Mechnikov who won the Nobel Prize for Medicine in 1908. In his Nobel lecture he described “white corpuscles of the blood…which absorb the microbes and destroy them” . The process of cell devouring is directed by molecular tags called opsonins which are produced by the body and stick to microbes. Imagine the microbe is a cookie: opsonins are like chocolate chips which make the cookie that much more appealing to the hungry neutrophil. Once consumed, the microbe is exposed to enzymes which kill and digest it.
The neutrophil’s second strategy, called degranulation, kills microbes occupying the local area. The neutrophil releases packets of enzymes which attack the outside of the microbe. This is like pouring boiling oil on invaders; crude but effective. Unfortunately this can cause collateral damage to the very tissue the neutrophils are meant to protect. The damage is limited because the neutrophils are designed to die 24-48 hours after moving into the tissue. As the dead neutrophils accumulate we can see evidence of them in the form of pus.
Even in death the neutrophil works to bring down enemy forces through its third killer creation: Neutrophil Extracellular Traps (NETs). NETs are a relatively recent discovery, outlined in 2004 by Brinkmann and colleagues. NETs are created once the neutrophil’s self-destruct programme has been engaged. DNA, proteins and hostile enzymes mingle within the cell which bursts open in a final kamikaze act that unleashes a web which can trap and kill bacteria. This works against an array of different bacteria, from Shigella, which causes dysentery, to Salmonella, which is responsible for typhoid fever.
Understanding this triad of killer skills is an important area of biomedical research. Neutrophils are designed to be part of a hard-and-fast response. If their assault is abnormally prolonged or excessive it can cause more harm than good. This process contributes to common autoimmune diseases including rheumatoid arthritis and emphysema. By understanding how neutrophils cause damage we hope to design new anti-inflammatory drugs to tone down the response and tackle these crippling conditions.
Yet we must not forget that we need neutrophils. Without their killer skills you couldn’t go for a stroll in a park or kiss someone without risking death by infection. This is a reality for people on certain chemotherapy regimes which decimate neutrophil numbers. Doctors can try to protect patients by putting them in dedicated isolation rooms and using stringent hygiene controls. However these are short term measures and what patients really need are their neutrophils. We can stimulate recovery of neutrophil numbers using medications that promote their production and therefore give patients their freedom back.
We’ve all heard of the villains – superbugs, anthrax, flesh-eating bacteria. We’ve celebrated medicine’s pharmacological victories like penicillin. It’s time we recognise the remarkable feats happening inside each and everyone of us every day. To uncover these mysteries it is imperative that we keep funding research in this tough economic climate – it took almost 100 years between finding phagocytosis and NETs. There is so much more to be found, and to find it we have to keep looking. Forget space, forget the ocean floor, the human body is a veritable treasure trove for scientific explorers and the spoils – improved quality and quantity of life – can be enjoyed by all. So next time you see some pus, take a second to marvel at those millions of superheroes and the scientists helping us to understand them.
. Ilya Mechnikov’s Nobel Lecture (Accessed 23/4/12)
Image: Neutrophil engulfing anthrax bacteria, taken with a Leo 1550 scanning electron microscope. Scale bar is 5 micrometers.From “Neutrophil engulfing Bacillus anthracis“. PLoS Pathogens 1 (3): Cover page. DOI:10.1371. November 2005.