Pac-Man Physiology

Yes, I admit it.  This Word on Health blogger has probably been spending way too much time recently think about blood cells. In the last week alone I have been re-learning basic anatomy and physiology as part of my paramedic course, providing training on infection control and cellular immunity to new emergency services recruits and preparing presentations on blood and coagulation disorders for one of our favorite clients.

So, it’s probably not altogether surprising that a news story about the expanded role of macrophages caught my eye.

For most of our readers, I suspect that the term “macrophage” conjures images of a hungry white blood cell gobbling invading bacteria, in a manner reminiscent of  the 1980’s iconic Pac-man.

It emerges however, that macrophages do much more than that.  Not only do they act as antimicrobial warriors, they also play critical roles in immune regulation and wound-healing.   Additionally, they can respond to a variety of cellular signals and change their physiology in response to local cues.

There has been a huge outpouring of research about host defense that has overshadowed the many diverse activities that these cells do all the time,” said Dr. David Mosser, Professor of Cell Biology and Molecular Genetics at the University of Maryland.  “We’d like to dispel the narrow notion most people have that macrophages’ only role is defense, and expand it to include their role in homeostasis.”

So what are macrophages?  Well, they exist in nearly all tissues and are produced when specialized white blood cells called monocytes leave the blood and differentiate in a tissue-specific manner. The type of macrophage that results from monocyte differentiation depends on the type(s) of cytokines that these cells encounter on their journey. Cytokines, for those not in the know, are proteins produced by immune cells that can influence cell behavior and affect interactions between cells.

For example, macrophages that battle microbial invaders appear in response to interferon-γ, a cytokine that is produced during a cellular immune response involving helper T-cells and the factors they produce. These macrophages are considered to be “classically activated.”

However, when monocytes differentiate in response to stimuli such as prostaglandins or glucocorticoids, the resulting macrophages will assume a “regulatory” phenotype.

Alternately, wound-healing macrophages arise when monocytes differentiate in response to interleukin-4, a cytokine which is released during tissue injury.

According to Dr. Mosser, macrophages can change their physiology and switch types. For example, in healthy, non-obese people, macrophages in fat tend to function as wound-healing macrophages. They are also thought to maintain insulin sensitivity in adipose cells. However, should an individual become obese, macrophages in fat will instead promote inflammation and cause the adipose cells to become resistant to insulin.  Similarly, immune-regulating macrophages produce high levels of the cytokine interleukin-10, which helps suppress the body’s immune response. Suppressing an immune response may seem counter-intuitive, but in the later stages of immunity it comes in handy because it limits inflammation.

According to Mosser, immune-regulating macrophages may hold the key to developing treatments for autoimmune diseases such as multiple sclerosis or rheumatoid arthritis. The focus of new research is on reprogramming the macrophages to assume a regulatory phenotype and prevent autoimmunity.

It might be possible to manipulate macrophages to make better vaccines, prevent immunosuppression, or develop novel therapeutics that promote anti-inflammatory immune responses.”

All of which kind of leads me back to the Pac-man analogy. In the video arcade game, when all the initial dots are eaten, Pac-Man is taken to the next stage where he gets to take on other enemies.   Here, despite the seemingly random nature of the enemies movements, they are in fact strictly deterministic.  Exactly, the same it seems, as it is with macrophages.

Suddenly learning Anatomy and Physiology may get a whole load more interesting for those back-to-school teens!