The Biology of Why We’re All Just Big Slime Buckets
Why, when, where and how our slime is created and what happens when things go wrong.
What’s the first thing you do when you have a runny nose?
Well, if you’re like me, you head for the medicine cabinet, drawer, or wherever you keep the stuff and look for some over the counter med to get rid of it, right! Cause blowing your nose into tissues or hankies for a day or so isn’t much fun, and your nose gets sore.
And now it’s out of sight and out of mind and you can forget about all that unwanted mucus for a while and get back to some kind of normal.
So let’s get one thing straight. You need to keep some slime (mucus) around.
If you have too much it’s big problems 😡
If you have too little it’s big problems 😡
You need just the right amount 😄 give or take a bit now and then.
In this article, I’ll look at our upper respiratory system to illustrate how and where mucus is made and by which cells, what its constituents are and how it works to protects us from infections and keeps our bodies operating like well-oiled machines.
Specifically, we’ll look at mucin genes and see how turning them on and off ensures that we maintain the amount of mucus we need for everyday usage. We’ll also see what happens when an infection is detected.
Lastly, we’ll look at the role that improper amounts of mucus plays in several diseases.
In Parts 1 and 2, I told you that mucus was made up of 2 major components, mucins and glycans. What I didn’t tell you was that you have a bunch of different kinds of mucins and there are genes that specify which mucin will be made at a given time.
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In this article, we’ll look at mucin genes and see how they ensure that we maintain the amount of mucus we need for everyday usage. We’ll also look at how they are turned on and off when an infection is detected.
All About Mucins
In the previous article, I talked a bit about mucin polymers and how they were the major structural component of mucus but I didn’t talk at all about the genetics of mucin.
There’s a fair number of mucin genes. Are they all present at the same time or do some of them only show up in certain situations or in specific tissues and organs?
According to the HUGO’s Human Genome Nomenclature Committee, there are 21 mucin genes and they fall into 2 broad categories, (1) those that produce mucins that are found on cell surfaces and (2) those that produce mucins that are large molecules that contribute to making the mucus and gels that we need to coat various tissues.
Where are all the mucins?
Let’s talk about where our bodies produce and use mucins and the gels they help to form.
Our body is made up of 4 different types of tissues;
It’s the epithelial tissue that produces the mucins.
Various kinds of epithelial tissues line both the outer and inner surfaces of our bodies. Examples are our epidermis or skin, the insides of our blood vessels and the outsides of our organs such as the trachea, lungs, kidneys, heart, liver, etc.
Specialized cells in our epithelial layers called Goblet cells produce the mucins. In the figure below you can see a photomicrograph of actual tracheal tissue on the right and a cartoon that explains what you’re looking at on the left. Let’s take a moment and really look at it so we understand it better.
The tracheal epithelial cells are the ones with the cilia at their tops and are sort of a salmon colour. The Goblet cells are the yellow ones filled with little balls of mucins and the small triangular purple cells form the connective tissue (basement membrane) and is where they are all attached to and anchored.
Then above all the cells, we can see 2 more layers; the watery saline layer and the mucus layer. We’ll talk about them a bit more below.
Pretty nifty, eh!
To get an idea of how important mucus is, let’s look at how our respiratory system manages mucus and mucins to keep all systems working properly and help prevent disease.
Your nose, pharynx, larynx, trachea and lungs make up your respiratory system or tract. It’s filled with a thick fluid, the airway surface layer also called the Epithelial Lining Fluid or ELF for short.
The ELF is actually divided into 2 layers, a watery saline layer that is in direct contact with the cilia which is where the cilia act to direct the mucus towards the pharynx, as shown in the diagram above, and a mucosal layer just above it. There are mucins present in both layers.
The 2 mucins most commonly found in this mucus layer are MUC5AC and MUC5B, named after the 2 genes that tell the goblet cells how and when to make them.
Interesting note: In the biology literature, symbols for genes are usually written in italics and the proteins that they encode and that are made from them are not italicized. So MUC5AC and MUC5B are the 2 genes that make the MUC5AC and MUC5B proteins.
So that’s the basic structure and where we find the mucus and mucins in our respiratory tract.
Ok, why do we have all this mucus? What does it do for us?
The Normal Role of Mucus
Mucus serves to protect and insulate human and other animal’s tissues from direct contact with their environment. The 2 biggest places in our body that this occurs is the respiratory tract and the intestines.
It acts in 2 ways to protect us:
- It coats the surface of the epithelial cell layer to prevent unwanted access.
- It cleans the surface by “washing away” infectious pathogens and debris.
Mucus is about 95% water. There are about 30 proteins that are found in mucus and a number of ions like chloride, calcium, sodium, bicarbonite and others. It is normally transparent and invisible but if it becomes infected, a yellowish or greenish cast is often noted.
A critical moment in the formation of mucus is the actual secretion from the Goblet cells or other glands that produce it. While still inside the cells, the mucin is packaged and condensed in a highly ordered fashion. Once it is secreted it rapidly expands over 1000-fold in volume! And this has to be tightly regulated so that it doesn’t get stuck in the channel the cell uses to excrete it. Without going into specific details, I’ll just note that this is accomplished by bicarbonate which removes calcium ions from the mucin during this process. The calcium ions are important to maintaining the packaging inside the cell.
Mucus is also home to a large number of commensal bacteria. These are part of what is often referred to as our microbiome. There are over 1000 species that take up residence in our large intestines in the outer colon mucus layer. These commensal bacteria do not normally cause a problem and in many cases, are quite helpful and necessary to our health.
In 2008, scientists found that the large intestine has a large inner layer of mucus that separates these bacteria from the epithelial cells. It’s when they breach this inner layer of defence that problems arise.
Diseases That Result From Mucus Disruption
As I mentioned at the beginning of this article, it’s important to maintain mucus levels within certain required limits or problems arise. And as I also said, the main causes of problems are either too much mucus or too little.
Let’s look first at diseases that arise from too much mucus as this is the most common problem.
This is a chronic condition and comprises sneezing, postnasal drip and a runny nose with no apparent cause. As you can see, all are due to excess mucus your body is attempting to rid itself of.
You are diagnosed with nonallergic rhinitis when allergens have been eliminated as the possible cause. It is more common in adults than children.
Some of the triggers include odours, medications, changes in weather conditions, certain foods and other chronic health conditions.
It differs from allergies because the immune system is not involved. Allergic conditions like hayfever etc. are caused by hypersensitivity and overreaction of the immune system.
The Common Cold
We all get them. Adults average 2–3 a year while children can get it 6–8 times a year. There is excess mucus. Your body is using it to eliminate the rhinovirus that caused it.
Again, sneezing, coughing, postnasal drip, runny nose, headache, sore throat and fever are the common symptoms. There is no cure for the common cold.
A Common Cold vs The Flu: They are 2 different diseases caused by 2 different viruses. Because they are viral, antibiotics are ineffective. Vaccination is effective against the flu because there are a limited number of strains and usually just a few are in circulation in a given season. Vaccination is not possible for the common cold because there are just too many viruses and strains that differ too greatly to construct a vaccine that would recognize them all.Luckily, except in rare cases where they can be life threatening, both are readily managed by our body's immune system without much, if any, residual damage to us.
Cystic Fibrosis is a very complex disease and to describe it completely is waaaay beyond the scope of this article. However, mucus does play a large role in people with this disease so we can talk a little about that.
Cystic fibrosis results from a mutation in the CFTR gene. The protein made from this gene plays an important role in producing sweat, mucus and digestive juices. It does this by helping to regulate salt concentrations on the inside and outside of cells.
In the respiratory system, the failure to properly regulate the amount of salt in the ELF reduces the watery saline layer (see our figure above) which results in the cilia trying to move the fluid in the mucosal layer, which is much thicker.
Because the mucosal layer becomes too thick for the cilia to wave back and forth to do their job of keeping the mucus moving, the layer increases in size and starts to clog small airways. This allows bacteria, which the cilia normally sweep out of the system, to increase in number, produce biofilms which “hides” them from the immune system and thereby produce repeated infections.
This leads to frequent chest infections and also results in the characteristic coughing and shortness of breath associated with the disease.
In 1959 most people died from the disease at about 6 months after birth. Nowadays, the median age of survival in North America is 40–48 years old depending on the patient’s gender and in what country they live.
Here’s a quote from the Wikipedia Cystic Fibrosis Page (bolding is mine):
“No definitive cure for CF is known, but diverse medications are used, such as mucolytics, bronchodilators, steroids, and antibiotics, that have the purpose of loosening mucus, expanding airways, decreasing inflammation, and fighting lung infections”
So we have come a long way in managing the disease and working with cystic fibrosis’ slime!
Asthma is another disease that involves increased levels of mucus in the airways. The airways are hypersensitive to particles like pollen or dust and when exposed, they become inflamed and produce excess mucus. The muscles around the airways tighten which narrows the space and breathing becomes difficult.
Etymology break: 😄 😄 If you’ve followed my posts, you know I love how scientific words were derived! From Wikipedia:“The word “asthma” is from the Greek ἅσθμα, ásthma, which means “panting”.”
Coughing during an attack may also bring up sputum from the lungs, which is hard to expel.
Asthma attacks are usually treated with drugs that open the airways (bronchodilators) and by reducing exposure to allergens and conditions that bring it on.
Chronic Obstructive Pulmonary Disease
Chronic Obstructive Pulmonary Disease (COPD) is similar to asthma in that the body produces too much mucus which makes breathing difficult.
One of the genes that is associated with COPD is CLCA1. When the CLCA1 protein is found in high concentrations in the airways, there is often an increase in mucus production.
It seems to work in conjunction with another protein, called TMEM16A. Dr Thomas J. Brett and his team found that when levels of CLCA1 increased, TMEM16A stayed on the surface of airway cells for a longer period of time.
In situations like the common cold, we also produce too much mucus but eventually, the infection is dealt with, we cough up the excess mucus as phlegm and everything returns back to normal. In COPD, there is so much mucus and it is in a state that resists removal by coughing. This means that the bacteria in this mucus is not removed and the infection continues. The immune system responds and this produces more inflammation which destroys more lung tissue. This ultimately results in death.
Interestingly, people in India have a very low frequency of ulcerative colitis. Yet, if they move to the United States, they have a much higher incidence of the disease.
Why is that so?
This disease is highly correlated with a person’s environment and diet. People with high fat and high sugar intake in their diet are more susceptible. When people come to the Western country, they alter their diet which results in increased disease rates.
How does disease arise?
In the colon, there are 2 mucus layers, an inner and an outer layer. If bacteria penetrate the outer layer, the first line of defence employed is immune system cells that seek out and destroy the bacteria. But if there are too many bacteria, the immune cells are outnumbered and overpowered. This allows the bacteria to enter and penetrate the inner mucosal layer.
This penetration is sensed by the underlying cells and they attempt to thwart the invasion by secreting even more mucus. But eventually, they exhaust the supply of mucus, fail to keep up with the bacteria and colitis results.
Eventually, the person recovers but then the cycle can begin all over again. Ulcerative colitis is known for its “coming and going” episodes.
Please note, I’ve given you a highly simplified and condensed version of what actually occurs but enough to appreciate the importance of the mucus layers in protecting our intestines and colon tissues. If you really want all the gory molecular details, this is an excellent review article by G. C. Hansson.
The tiny branching airways in the lungs are called bronchi. If the tissues and muscles that surround bronchi are damaged or destroyed, then the bronchi become wider and more mucus accumulates in them.
As we’ve seen above, the increased amount of mucus leads to higher levels and frequencies of infections. In turn, these may damage more bronchi and over time, the cycle leads to a worsening of the condition.
In the UK, the rate of disease is about 1 in every 1000 persons and the majority of these cases were in people more than 60 years of age.
What about not enough mucus?
In Sjögren’s Syndrome, the exact opposite of the diseases discussed above occurs; not enough mucus is produced.
Similar to asthma, this disease is a result of a malfunctioning immune system thus it falls under the category of autoimmune diseases like lupus and rheumatoid arthritis. The person’s immune system attacks the glands that provide saliva to the mouth and tears to the eyes. This can damage the cornea and result in a reduction of vision.
It can also affect other parts of the body. From the article linked above:
Other parts of the body where there are mucous membranes also begin to dry out. This includes the nose, throat, lungs, vulva and vagina. Drying in the lungs can result in lung infections or pneumonia. There may be a loss of hair on the body.
And voila, that does it for the conditions intimately associated with mucus that I wanted to profile. There are other conditions but the ones I talked about are the most common ones.
Now we know a little bit more about the crucial role that mucus plays to maintain the health of our bodies and the tissues and organs within.
Once upon a time, mucus was thought to be pretty boring stuff. Just obnoxious slime to be dispensed with as rapidly as possible. Now you know differently and that’s a good thing.
Ok, Guess what? When I started out writing about mucus, I thought it was going to be a 2 part series.
Boy was I wrong!
Maybe it’s a 4 part series or even more. Who can predict how things evolve sometimes?
In Part 4, I’ll talk about how mucus evolved and some of the roles it plays in other creatures on this amazing slimy planet.
Until next time,
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