About Neutrophils

The neutrophil is also a phagocytic (eating) cell like the macrophage (as we discussed in the previous blog post). While macrophages reside in the tissues exposed to the outer world, neutrophils can go anywhere they are needed. They are transported by the blood in arteries and veins. In fact, the blood is a perfect vehicle as blood vessels do not leave a single cell out when they deliver food.

They exit the blood and head over to the battle scene in minutes after they are called. Like macrophages, they use strong chemicals to destroy their prey after taking them in. In addition, neutrophils are also allowed to pour those chemicals out and turn the surrounding tissues into a "toxic soup". On one hand, this creates a lethal environment for invaders. On the other hand, it causes a damage normal tissues. In fact, this collateral damage can explain why neutrophils have a short lifetime (i.e., about five days). In contrast, macrophages live for months.

Exiting Blood

Normally, neutrophils are flowing along with the blood in the blood vessels at a high speed. At any point, macrophages encountering with an invader can produce signal alarms to call neutrophils to the battle scene. To have neutrophils stop and exit the blood in order to be delivered to the battle scene, adhesion molecules are used.

An adhesion molecule called selectin is produced and positioned on the surface of endothelial cells (cells lying on the inner wall of the vessel), when they receive the alarm signal from the macrophage. This molecule adheres to another adhesion molecule, SLIG (selectin ligand) that is found on the surface of neutrophils. The interaction between these adhesion molecules causes the neutrophil to slow down and start to roll along the inner surface of the blood vessel (see the picture below).

When the slowed down neutrophil receives the alarm signal, it starts to express an adhesion molecule, integrin, on its own surface. Once integrin appears on the surface of the neutrophil, it interacts with its adhesion partner, ICAM, which always is expressed on the surface of endothelial cells of the vessel. This interaction is strong enough to stop the neutrophil (see the picture below).

Once the neutrophil is stopped, chemoattractants -- chemicals that attract needed molecules to the battle site -- make the neutrophil exit the endothelial cell and travel to the battle scene. Chemoattractants include C5a -- a complement system protein, which you might remember from this post -- and formyl methionine (f-met) which is a fragment of bacterial proteins. These chemoattractants help the neutrophil find the invader (see the picture below).

Lessons for Cybersecurity

The successful delivery of neutrophils depends on expression of two different adhesion molecules and it might look redundant and slow. But being dependent only on selectins for exiting the blood might not be in our favor in situations where a single endothelial cell mistakenly starts to express selectin proteins.

Also, it takes about six hours for selectins to be produced and expressed by endothelial cells after receiving the alarm signal. Even though it seems like a slow process, this slowness is needed to give time to macrophages handle the attack by themselves. If attacks lasts for more than six hours, only then the attack can be seen as serious so that neutrophils can take the stage.

References

1. Sompayrac, Lauren. How the Immune System Works. Fifth ed., John Wiley & Sons, Ltd, 2016.