Absolutely different thing is hemodynamic oedema,
which can occur without any inflammation.
For example, under tourniquet or in thrombosis
of vein as a result of pure hemodynamic venous condition,
but without inflammation and without production of inflammatory mediators.
In that case, we also have increase
in pressure gradient and we have transudation process.
But we have no inflammatory mediators,
we have no activation
of transcytosis and we have no increase in vascular wall permeability.
So the difference is that hemodynamic oedema depends on transudation
exclusively and inflammatory oedema depends on
both exudation mechanism and transudation mechanism,
which is increase in permeability and increase in pressure gradient.
This results in the difference of the content of oedematous fluid in exudation it
contains much more protein and much more of proteins with large molecules.
The next thing is the mechanism of white blood cell transmigration.
You can see this mechanism in this picture.
In short, it consists of several stages like capture of leukocyte,
rolling of leukocytes along the vascular wall, slow rolling,
adhesion and the transmigration across the wall.
Basically, all these processes are molecular and they depend on
consequentive multi-step expression and
activation of cell adhesive molecules (CAM).
Cell adhesive molecules are expressed under the influence of
inflammatory mediators both on white blood cell and on endothelial sites.
And they bind each other as a result of that,
we can observe these cellular events.
The decisive role, in this behavior of white blood cells and endothelium belongs to
so-called selectins and their ligands so-called PSGL molecules.
Also, the next phase of cell margination and transmigration depends
on cell adhesion molecules named integrins and
their ligands immunoglobulin like adhesive molecules or ICAMs.
You can see the interaction between ligands in this picture.
The emigration of white blood cells out of
the blood vessels in inflammatory foci was observed long ago.
Here you can see French scholar Rene Joachim Henri Dutrochet,
who observed emigration of leukocytes very early in the beginning of 19th century.
But to that moment unfortunately,
leukocytes and their functions were not yet discovered.
That's why Dutrochet made
that discovery but interpreted his own discovery absolutely wrong.
He decided that this are just erythrocytes from
the damaged blood vessels and these erythrocytes just bleached
out or get pale losing its pigment because of inflammation.
So, he did not recognize that these were white blood cells who emigrate.
Red blood cells do not express integrins,
selectins and are not able to overt cellular events.
Now to finish about the mechanisms of
white blood cell emigration and the adhesion phenomena,
look at this detailed picture and you
can see here that the process consists of several steps.
First step is rolling,
next step is integrin activation by chemokines and finally it
comes to stable adhesion and migration through endothelium.
And in every step new and new cell adhesion molecules are involved.
Initially these are Sialyl-Lewis
X-modified glycoproteins on the leukocytes and P-selectins,
E-selectins on endothelial cells.
After that integrins are involved and
finally various cell adhesion molecules related to
extracellular matrix of the surrounding connective tissue.
Now few words about the about
the difference between different emigrating white blood cells.
These are granulocytes, among them neutrophils
and agranulocyctes among them monocytes, macrophages.
Both are able to phagocytosis but they have different tasks,
different abilities and different roles in acute inflammation.
Here you can see,
from the left side you can see
predominantly neutrophilic exudate and from right side in that picture you can
see predominantly Mononuclear macrophago and Lymphocytic infiltration.
Neutrophils are first coming into the foci in acute inflammation and you can
see in this plot that the peak migration of macrophages is a little bit delayed.
It occurs a little bit later compared to neutrophils.
Neutrophils, the main disinfecting agents.
Lymphocytes or macrophages are not able to
establish disinfection because they are not able to
produce such a huge amount
of bacteroides other reactive oxygen species which are produced by neutrophils.
So neutrophils, their task is disinfection.
Also, it is related to the unique activity of
their myeloperoxidase enzyme and to production of
hypochlorite anion or perchlorate anion in them.
Macrophages are not able to establish that.
So neutrophil is a cell with strongest oxidative burst,
strongest oxidative stress and that's why neutrophil never survives after phagocytosis.
Lifetime of neutrophils is 48 hours,
24 hours in bloodstream and 24 more hours in tissues.
Either it bursts and perished as a result of phagocytosis and inflammation,
or it is extinguished
by means of apoptosis within that 24 hours.
If you will ask me,
"what is the difference between neutrophil and Macrophage as regards to defense?"
I will compare neutrophil with hand grenade in militaries,
you throw hand grenade into your enemy and enemy is killed but
a hand grenade also is broken into pieces and no longer exists, that is neutrophil.
It is like hand grenade attacking and victimizing its own life.
So it is short living participant of inflammation.
Another thing is macrophage,
macrophages are long living cells.
These are clever conductors of inflammation
and they take part in remote phase of inflammation,
even in chronic inflammation they will be predominating.
Macrophages are not able to disinfect and even they can harbor alive microbes,
they can harbor germs and even they can facilitate the spread of infection.
But they are able to produce all groups of inflammatory mediators
and they are responsible for a switch from acute into chronic course of inflammation.
Also, they are able for reparative process,
for fibroblast stimulation, for fibrosis.
They are able to present antigens to
immune system and conduct the immune process.
This is not the case for neutrophils.
Neutrophils are just hand grenades of inflammation but macrophages are like
cannons with a set of various shells for different military purposes.
So if you will remember that macrophages are also able to control fever which accompany
inflammation because they produce a lot of
endogenous pyrogens, provoking fever.
We may say that macrophage has
broadest repertoire of phagocytosis and broadest set of functions in inflammation,
compared to neutrophils which have relatively narrow purpose just to kill,
just to provoke disinfection and die.
