The immune system is like an army keeping us safe from invasion, injury and infection and helps us to regenerate and repair tissues and organs. However, the immune system is sometimes a double-edged sword that does more harm than good.
A lot of focus has been on the role of macrophages and their ability to facilitate tissue healing and regeneration. Today, we will be looking at a new mouse study that examines the role of neutrophils and how they can actually harm the brain further following a stroke.
A double-edged sword
Neutrophils are white blood cells created in the bone marrow and are generally the first responders to attack and injury. They are like soldiers and arrive at the first sign of microbial invasion, and they head to the site of injury as fast as possible so they can destroy the invaders.
This is great because it means that the body can mount a rapid defense the moment there is an infection, helping us to fight off illness and injury. However, when the injury is an intracerebral hemorrhage, a type of stroke caused by bleeding within the brain tissue itself, neutrophils rush to the site of damage expecting a battle, only to find that there is nothing to fight.
At this point, unless the neutrophils are removed straight away from the brain by other types of immune cells, they start causing damage and use their range of toxic chemicals normally used on invaders on the brain instead. Therefore, their presence actually increases the damage caused by this type of stroke, making the injury more severe.
Stand down, soldier!
Researchers at The University of Texas Health Science Center at Houston have found a way to temporarily suppress neutrophils to stop them from deploying their chemical weapons and change their behavior so that they scavenge for toxins instead. This means that there is the potential to use this as a therapy for hemorrhagic stroke treatment.
When a hemorrhagic stroke happens, an artery inside the brain leaks, causing bleeding into the brain. It is the second most common type of stroke, with ischemic stroke being the first; it also has a mortality rate as high as 67 percent and is a leading cause of disability in adults. The compression of the brain, caused by blood leaking from into the brain tissue, and injury resulting from factors in the blood are the main causes of damage.
Around half of hemorrhagic stroke victims die within two days, and researchers believe that secondary damage, such as from iron toxicity from the breakdown of red blood cells, leads to excessive levels of inflammation caused by increased free radicals in the brain.
The neutrophils can produce chemicals that can cause injury, but they can also create helpful ones, such as lactoferrin, a protein that binds iron molecules, removing it from the system.
As neutrophils prepare to attack, the brain and spleen produce interleukin-27, a molecule that signals the neutrophils to produce lactoferrin to help facilitate tissue repair and recovery. However, this can take between 12-18 hours before the body does this and switches the neutrophils from attack to healing, and this is all too often too late for stroke victims.
Treating neutrophils directly with lactoferrin appears to be effective in switching them from an attack type (polarization) to a type that facilitates healing and removes toxins from the injury site. In short, the researchers here speed up the natural switch to the healing instructions the body gives by directly introducing the chemical orders it gives its soldiers.
The research team is now working on an improved form of lactoferrin that is able to penetrate the brain faster and more efficiently.
The manipulation of immune system cells to facilitate healing has been a hot topic this year, and macrophages, T-cells and now neutrophils have all had their behaviours beneficially tweaked in a number of studies.
The immune system is an amazing thing, and if we can improve on how it works, it could hold the key to regenerating damaged tissue and helping people recover from strokes and many age-related diseases. Let us hope that these results in mice translates to humans in subsequent clinical trials.
 Xiurong Zhao, Shun-Ming Ting, Chin-Hsuan Liu, Guanghua Sun, Marian Kruzel, Meaghan Roy-O’Reilly & Jaroslaw Aronowski (2017) Neutrophil polarization by IL-27 as a therapeutic target for intracerebral hemorrhage Nature Communications 8, Article number: 602 doi:10.1038/s41467-017-00770-7.