The GcMAF Book

Chapter 6

Your Awesome Macrophage Killing Machine

Macrophages are big and smart white blood cells that chase, capture, engulf, and digest intruders. They trap and phagocytize (literally, “eat”) their enemies. They can multiply rapidly when necessary. However, they’re naturally indolent and need to be activated by GcMAF. Opsonin “super glue” helps them stick to their prey. Their electron-driven free radical death ray (AKA “oxidative burst”) blasts holes in microbes and cancer cells. Once a microbe or cancer cell has been phagocytized by a macro, it is encapsulated inside a “phagolysosome” (the intracellular “death chamber”), where it is then killed (if it isn’t dead already), and then dissected down into its component parts, which are then recycled.

Although I have already described macrophages, these large immune cells are so important in terms of understanding how GcMAF works that I need to go into a little more detail about them. Besides, they are truly fascinating critters!


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A macrophage


If you could imagine a living, breathing, oozing, cunningly horrific humongous sticky blob that combines the dangerously diabolical features of King Kong’s intimidating size, Hannibal Lechter’s cannibalism, Darth Vader’s lightsaber, The Terminator, Bruce Lee, and the Marshmallow Man that takes over New York City in Ghostbusters—all rolled into one giant killing machine—you’d have some idea of what a macrophage is all about. They’re big. They’re nasty. If you were a bacteria, virus, or cancer cell, you would do your darnedest to avoid them.

As cells go, macrophages are huge

How big is a “Big Mac”? By way of comparison, red blood cells, white blood cells, and typical cancer cells are about 7 microns (micrometers or millionths of a meter) in diameter and have a volume of about 250 cubic microns. At about 20 micrometers (20 millionths of a meter) in diameter, macrophages are about three times as wide as regular cells. But, because a little extra width translates into a lot of extra volume, macrophages—at around 4000 cubic microns—have about 16 times the volume of normal sized cells. If a cancer cell were the size of a Toyota pickup, a macrophage would be bigger than an 18 wheeler.

Not a dumb truck

But this behemoth is not a dumb truck. Bristling with weaponry, it’s stuffed to the gills with a daunting array of high-tech systems programmed for a singular purpose: take out the enemy as quickly and efficiently as possible. We call this “tumoricidal capacity.”

Here’s how it works. When it isn’t swimming in the blood stream, a macrophage can slowly “walk” through tissues using self-generated stumpy little (one micron) “legs” (about ten of them sprout at a time). The macrophage ambles over to and snuggles up alongside a “foreign invader” (e.g., cancer cell or virion), quickly identifies it as foe, sprays it with membrane-frying free radical-laden Darth Vader death beams, grabs, engulfs, smothers, kills, and digests it. If the enemy is further away, or trying to escape, the macro chases after it, extrudes a cluster of long thin sticky spaghetti-like tentacles that wrap around and ensnare the fugitive cell, clutching it in an unbreakable strangle hold.

In a process known as phagocytosis, the macro draws in its victim, engulfs and smothers it, then encases it in a small bubble-like cyst (called a phagolysosome) inside its cytoplasm. The phagolysosome then secretes a cocktail of corrosive free radicals and enzymes that rapidly digest its victim down into its component parts (amino acids, nucleic acids, fatty acids, etc.). The macrophage then spits out these pieces into the intercellular “soup. ” Because the remnants of viruses and cancer cells are fundamental cellular building blocks, the body quickly recycles them using the “spare parts” to build brand new healthy cells.

I finding it totally amazing that this complex and truly violent scenario is unfolding in you and me billions of times per minute.

A review of the macrophage’s most important weapons:

Pseudopods

Literally “false legs.” These can be short and stumpy, e.g., like the ones macros make in order to “walk” along the inner lining of blood vessels. For chasing and grabbing fugitives, however, macros can make much longer pseudopods that extend out relatively large distances (perhaps 60 microns). Imagine a macro the size of a Volkswagen with the capability to extend hundreds of long thin arms (each about the diameter of an exhaust pipe) out to 50 feet or more. Once out there, they can weave themselves into a net that tangles around and traps the hapless enemy. If that target were a cancer cell, it would be about the size of a motor scooter. If a bacterium, it would be about the size of a roller skate.

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Macrophage ensnaring bacteria

Phagocytosis and phagolysosome formation

Once the pseudopods have ensnared their victim, the engulfing process ensues. The outer membranes of the pseudopods nearest the microbe or cancer cell simply merge into one another so that the victim is completely surrounded and encapsulated in what is called a phagolysosome. (“Phago ” means “eat,” “lyso” means “digest,” and “some” means “cell” or “body.”) Amoeba-like, the macrophage has reshaped itself such that the phagolysosome lies deep inside. Then the membrane that makes up the wall surrounding the phagolysosome shoots more death rays at its captured prey (just to make sure it is dead), and proceeds to digest it with an array of corrosive enzymes. More about phagolysosomes in a minute.

To see a cool video of a white blood cell (a neutrophil) chasing and phagocytizing a bacteria, go here:

http://www.youtube.com/watch?v=MgVPLNu_S-w&NR=1

(This is a neutrophil, not a macrophage; a macrophage would be about 16 times larger.)

Opsonins: Super Glue “binding enhancers” that help macros latch onto enemies

To help them grab and hold their victims, macrophages send signals to nearby lymphocytes, instructing them to spray a thin coating of sticky proteins onto potential prey. Then, when the macro’s long thin arms make contact with the microbe or cancer cell, this “super glue” coating hardens, making it impossible for the desperado to shake loose.

Typically, a macro sends out a cluster of (say twenty or so) sticky pseudopods that surround the enemy cell, encasing it in a mesh like affair, not unlike a large fish net, in which the microbe or cancer cell becomes ensnared. Like a fly in flypaper, the enemy cell is both stuck in it and to it, so there is no way to get loose. Then the prey is gradually surrounded and engulfed, ending up snugly inside the macro as a phagolysosome, in which it spends its last few moments as a life form before being digested down into its component parts by various free radicals and enzymes.

The sticky proteins are called “binding enhancers” or “opsonins.” The gluing process is called “opsonization.”

Interestingly, when a macro grabs an enemy this way, it wants its fellow phagocytic soldiers to know prey is nearby, so—like an isolated soldier who has stumbled upon a group of enemy troops and is calling for backup— it sends out protein signals telling nearby macrophages to make more of the receptors that specialize in grabbing specifically that kind of enemy. There’s safety in numbers. (Technically this is called “upregulating expression of complement receptors on neighboring phagocytes.”)

Electrons death ray beams from the “oxidative burst”

Because it is so diabolically sophisticated—and right out of Star Wars—my favorite macrophage weapon is the “oxidative burst” (also widely known as the “respiratory burst”). This is the Darth Vader death ray. An enzyme (called NADPH oxidase) stationed in the macro’s outer membrane sprays out a beam of highly reactive free electrons, like bullets from a machine gun.

Remember those old TV sets with picture tubes? The NADPH gun is kind of like that. At the back of the tube an electron gun aimed particles that hit phosphorescent particles on the screen. When the electron beam hit the particles, the screen lit up, creating a picture. Likewise, NADPH also emits a particle beam. But instead of playing Howdy Doody, it’s blasting tumor cells and microbes to smithereens.

The electrons in the beam emerge one at a time, but they really really don’t want to be “free,” so—as fast as they possibly can—they snatch another electron to form a stable pair (we are talking nanoseconds here). A chain reaction of electron-snatchings triggered by the oxidative burst literally vaporizes molecules in the outer wall of a cancer cell or viral capsid, ripping holes in it. Now the membrane that held the victim together literally falls apart, spilling out its contents. Without an intact outer membrane, a cancer cell can’t survive for very long.

Oxidative bursts don’t happen all of the time. That would be a waste of firepower. The “trigger” that turns it on is the perceived proximity of a “foe,” a cancer cell, HIV virus, hepatitis virus, or a bacterium. When a macro comes into immediate contact with “enemy,” then—and only then—does it turn on the electron death beam.

There are lots of oxygen (O2) molecules everywhere in our bodies. (We need plenty of oxygen and glucose, the “fuels” from which we generate the “energy” that drives all of the cellular chemical reactions that make life possible.) When released, most of the electrons in the death ray beam crash into one of these omnipresent oxygen molecules, from which they quickly grab the electron they need to make a stable pair. The oxygen molecule now is missing one of its electrons, and is thus transformed into the violently corrosive free radical known as “superoxide” (O2-). Now superoxide is the one wanting an electron, and it will destroy anything in its path to get one. That “anything” would be the virus, bacterium, or cancer cell our macro has grabbed with its pseudopod. Suddenly the invader finds itself with a huge hole in its outer membrane. It’ll die soon.

The free electrons and superoxides also trigger chain reactions forming other reactive free radical species. One of these is the hydroxyl ion (OH-). This is hydrogen peroxide, just like the stuff that comes out of that brown bottle, but 33 times as potent—a locally generated intercellular dose. Perfect for frying microbes and tumor cells.

By oxidizing omnipresent chlorine atoms, the electron beam also generates noxious hypochlorous acid (HClO), which can poke a hole in an enemy membrane in nothing flat. Now we have a toxic soup of free radical oxidizing agents that can do tremendous local damage to our enemies.

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“Wait a minute,” (I can hear you saying,) “how come our own cells aren’t damaged by friendly fire? How do they escape the death rays?” Great question. We have a protective shield that prevents the free electrons and free radicals from damaging our own cells. It’s called SOD (superoxide dismutase) and it’s an enzyme (a large protein molecule) that specializes in neutralizing superoxide and other free radicals before they can damage our own cells. For maximum protection, SOD is positioned right next to the NADPH death ray generator proteins in the outer cell wall (or membrane) of our macrophages.

The “barrel” (the NADPH molecule) of the macro’s electron-generating death ray gun is aimed toward the outside of the cell and sticks out of a little hole that is surrounded and protected by molecules of SOD, forming a kind of “bunker” to protect the electron gun and your macrophage cell. As long as we keep making SOD (and we’d be dead in minutes if we stopped), we’ll be safe; the electron beam can’t harm us. It’s a pretty cool combination: a ridiculously deadly weapon with built-in safeguards for the user (that would be you).

GcMAF-Activated Macros and the “Oxidative Burst”

You’ve heard this before, but I have to say it again: only GcMAF- activated macros are going to deliver oxidative bursts that are potent enough to be effective. If Nagalase from viruses or cancer cells has put the macros to sleep, the oxidative burst degenerates into a piddly potato gun that’s not going to hurt anybody. Firepower—or lack thereof—is what we are talking about here. Remember those old westerns in which six-shooters were the main weapon? There’d be a shot here, long pauses, and then another shot over there? There was a long enough gap between shots that you could actually hear the ricochets. That’s a de-activated mac: slow at the draw and not getting very many shots off. Reloading after every six shots. No wonder the Indians creamed Custer. Activated macros fire the atomic equivalent of millions of rounds a second and never have to pause to reload. Some newer movies have so many bullets flying from so many directions that it is hard to understand how anyone could survive. That’s firepower of the sort only GcMAF-activated macrophages could deliver.

The Phagolysosome execution (and dismantling) chamber

If, somehow, a microbe or cancer cell has survived the oxidative burst and phagocytosis, it will not survive the death chamber. Once eaten, internalized, and embedded in the macrophage’s cytoplasm, the enemy is imprisoned in a round cyst-like bubble inside the macrophage (called a phagolysosome) into which are squirted all sorts of digestive enzymes and many more rounds of oxidative burst, just for good measure. Pretty things do not happen inside of phagolysosomes. If the cancer cell or microbe is not already dead, the phagolysosome “death chamber” will certainly polish it off. (“Phago” means “to eat.” “Lyso” means “to dissolve.” “Some” means “sack” or “bag.”)

Once the dismembering process is complete, the phagolysosome slides over and makes contact with the outer cell membrane, merges with it, then disgorges the now harmless breakdown products (nucleic acids, fatty acids, amino acids, etc.) out into the extracellular fluid. They are then taken up by nearby cells and recycled into new body parts. The ecologically-minded among us should find the efficiency of this process commendable. Nothing is wasted. Scary toxic bad guys are killed, dismantled, and transformed into spare parts for the good guys: us.

A sophisticated communication system

Talk about communication systems! Immune cells—macrophages and lymphocytes— carry on a constant blather, like a huge town hall chat room where everybody is talking at once. However, since the talking is a release of “messenger molecules” and the listening is done by protein receptors, immune cells can actually listen while they are talking!! No need to complain about being interrupted! It’s weird, and foreign to us humans, but this simultaneous talking and listening makes for a far faster exchange of messages than if you had to stop and listen every time the other guy was talking (like we humans usually do).

There is so much activity, what with the constant molecular chatter coupled with a madhouse of cellular scrambling to grab and kill enemy cells as rapidly as possible, that the casual observer might get the impression of chaos. But she would be sadly mistaken. There are no wasted efforts here. Like a Beethoven symphony, everything is extremely well-organized and perfectly coordinated.

The chemical chatter among macrophages and other immune cells is so rapid and efficient that it would make a sophisticated military communications system look like a bunch of kids with tin can phones. Macros release clouds of messenger molecules (cytokines, interferons, leukotrienes, and other small molecules)—at rates of up to thousands of molecules per second per cell. Each molecule carries a specific request or command. Like “Bring me this,” or “We need some of that over there,” or “Kill everything that looks like this.” “We need an inflammatory response over here.” Or “We don’t need to do that anymore.” They discuss what the enemy looks like and how aggressive he is. They tell each other how hard to work. They label targets for other cells to identify and kill. They talk about where the enemy is hiding. They discuss current enemy strategy and how best to outmaneuver it.

Exponential self-cloning: the ultimate weapon

Last, but definitely not least, macros—if outgunned—play the population card: they multiply rapidly. When they find themselves in an area of high cancer cell or viral particle density, they don’t have to call up the draft to get more troops; they simply clone themselves, which they can do on very short notice. More macros automatically translates into more of all the other weapons enumerated above. But, again, this multiplication process occurs only in activated macros.

GcMAF Activation

Without GcMAF, macros languish. In the presence of GcMAF, their activity level increases exponentially. Once activated, macros multiply rapidly and attack ferociously. In the following chapter, I explain why…

Copyright © 2010 Timothy J. Smith, M.D.