_W_E_A_P_O_N_S - OF - W_A_R_

WEAPONS
OF
WAR

Staff Sergeant Skip Dee skillfully & stealthily closes in on the enemy stronghold – a lawless group of German soldiers held up in the basement of an old, dilapidated stone house built sometime in the early 1800’s. After carefully casing the old fortress, Skip notices a broken window pane and peering in through the window is a long, dank hallway with slatted wood flooring. About 30 feet away is an opening in the flooring, a crevice just large enough for a hand grenade to fall through and wipe out the enemy. Having been a star baseball picture in high school as well as a promising minor league baseball player before being drafted into the war, Sergeant Skip was reasonably confident that he could hit that mark w/ the grenade. Sgt Dee made his pitch and deftly threw the grenade through the opening, watched it hit the floor, roll along and almost come to a complete stop when it made one final rotation and fell into the crevice he was aiming for.

We’ve got stuff like that in going on in our own bodies on a regular basis. Instead of hallways, we’ve got blood vessels. Instead of hand grenades, we have leukocytes. Our munitions and manufacturing for many of these weapons is done safely and discretely in the depths of our bones, in the bone marrow. We may not always have holes in our blood vessels but we do have an arsenal of weaponry which can increase the permeability of our blood vessels at a moments notice.

Instead of Germans, let’s say we have uninvited bacteria in our system. That’s enough to get the ball rolling or, in this case, the leukocyte rolling …literally. A leukocyte is a white blood cell.

Oh, and Herr Bacteria, did you really think you could hide? Think again. You can’t go more than two cells in the human body with out running into a capillary and those blood vessels are the leukocytes conduit – the transportation system which will deliver your impending doom. Silly bacteria, the cells which make up the walls of the blood vessels are easily alerted to your presence.

Here comes the hand grenade in the form of a leukocyte – a big white sphere of destruction. The smaller, faster moving red blood cells tend to push the leukocyte towards the walls of the blood vessels and once it hits the wall it’s going to start to roll – literally. And then, the white blood cells is going to stop ….then it’s going to start to seep through the wall of the blood vessel – it knows you’re out there – that’s why it stopped where it did. It’s going to seep through the wall and then destroy you!

There’s so much of a story with the human body it’s hard to know where to begin but, let’s start with that rolling and seeping of the leukocyte. Yeah, the military has C4 but, we’ve got C4 too and that’s just the beginning.

The reason that white blood cell starts to roll along the blood vessel wall and begin it’s adhesion is due to a family of molecules known as Selectins.

Military: C4, X-15, F-16 hornet, ….yawn….

HUMAN BODY:
Selectin Family:
CD62E aka E-selectin, found on endothelium (that’s what vessel walls are made of)
CD62P aka P-selectin, found on endothelium & platelets
CD62L aka L-selectin, found on surface of most leukocytes

I know what you’re saying… CD62E, P & L aren’t ALWAYS there, are they – other wise our white blood cells would always be rolling and starting to stick all over the place. Well, of course not! We’re smart & in a brilliantly manufactured, supremely designed bod. Remember – The bacteria started it! Normally, P-selectin would be quietly held in inside the cells in nice little homes called Weibel-Palade bodies BUT, the bacteria provoked us – it started the fight! Histamine and thrombin has a tendency to wake up things like P-selectin. Similarly, E-selectin isn’t looking for any trouble either but, bacteria also up IL-1 (interlukin 1) and TNF (tumor necrosis factor) which, in turn, caused E-selecting to come out of hiding.

Now then, we said the leukocyte came to a stop ….yeah – that’s pretty cool also. How does it know where to stop? It now gives me great pride to introduce another family and, this isn’t just any family…it’s a SuperFamily! Ladies and gentlemen, straight from you’re very own intermolecular make up, allow me to introduce ….the IMMUNOGLOBULIN SUPERFAMILY!!!!

Military: ICBM (intercontinental ballistic missle), NORAD

HUMAN BODY:
Immunoglobulin Superfamily:
ICAM-1, intercellular adhesion molecule 1
VCAM-1, vascular cell adhesion molecule 1

TNF & IL-1 induce the expression of both ICAM-1 and VCAM-1. The superfamily resides on the endothelial cells. Integrins are expressed on the leukocyte cell surface and the Superfamily and Integrins are going to hook up! This hook up is what causes the leukocyte to finally stop rolling and finally settle down, maybe meet a nice leukocyte of the opposite sex and see if it’s not too late for a little mitosis action – oh wait, that’s a different story.

What is an Integrin? Why they are transmembrane heterodimeric glycoproteins of course! Now, aren’t you sorry you asked? But really Sally, Integrins are just pieces on the wall of the leukocyte cell that are going to hook up with the superfamily, that’s all. Yeah, but I bet the Integrins have really cool names that go with them, don’t they? They sure do Bill! Just check out this list of binding integrins….

HUMAN BODY:
Binding Integrins for ICAM-1:
LFA-1 (CD11a/CD18)
Mac-1 (CD11b/CD18)

Binding Integrins for VCAM-1:
VLA-4

OK – keep things clear here. The ICAM and VCAM are members of the Superfamily which reside on the blood vessel walls - and the Integrins are what pokes out of the leukocyte cell walls. Maybe ICAM is a little fickle, I don’t know but he sure seems to like BOTH LFA-1 and Mac-1. VCAM is a little more reasonable and just goes for the VLA-4 ….maybe VCAM is a purist and only likes other entities which start with the letter V. who knows.

What we have here is a very small glimpse into the Pathology of Warfare as presented by the human body and concludes our hand grenade story but allow me to preview a glimpse of coming attractions…

In the military we have divisions commonly known as as Air Force, Army, Marines & Navy. Don’t think the leukocytes & human body is outdone because it has it’s own divisions of Leukocytes known as Lymphocytes, Granulocytes and Monocytes. These subdivisions also have their own unique brand of special forces just as the military has it’s Green Beret’s and Navy SEALS.

Lymphocyte Special Forces include
B cells,
T cells,
Natural Killers (NK’s)

Granulocytes Special Forces:
Neutrophils
Eosinophils
Basophils

Monocyte Special Forces:
Macrophages (several different types)