Inflammation always follows a certain procedure as the picture below demonstrates, and it involves two separate mechanisms: one involving the recruitment of white blood cells, and the other involves the movement of fluid from within blood vessels towards the outside, otherwise known as the formation of transudates and exudates. This is done to both clean up dead cells and to get rid of foreign substances that may have entered the body. Neutrophils are the first cells that are involved in the inflammatory process: after that, phagocytes such as macrophages take over. Here’s a Youtube clip for you that I’ve found handy which is a lecture-styled discussion of the inflammatory response: Inflammatory Response.
Recruitment of White Blood Cells There are four stages involved in the recruitment of white blood cells:
- Margination, adhesion to the endothelial cells at the edge of the blood vessel, and rolling along the vessel wall
- Firm sticking to the vessel wall (known as the endothelium)
- Squeezing between the gaps in the cells
- Migration of the cells to the target by means of chemotaxis.
Margination and Rolling
The larger white cells are moved at a slower rate along the capillaries than the smaller red cells, and they tend to be pushed along the vessel walls due to laminar flow (flowing in parallel lines within a pipe, as the picture alongside demonstrates). The process of the white blood cells being pushed against the vessel walls is known as margination. As the white blood cells end up on the wall, they ‘roll’ along the wall and stick briefly along the way via adhesion molecules, hence putting the brakes on the movement of the white blood cells. Examples of these adhesion molecules are selectins, and they include E-selectin, P-selectin and L-selectin. These only tend to appear around sites of injury and are not seen on cells that are uninjured.
Adhesion (Sticking) White blood cells then stop completely by sticking firmly on the cells via integrins. These
integrins are activated by chemokines (chemicals known as cytokines which are released during the inflammatory process). At the same time, ligands such as ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) attach to the integrins. These processes together cause the integrins to become high affinity (make the key fit better in the hole, in other words). Migration The white blood cells gain access to the extracellular space outside of the blood vessels through the intercellular junctions. This process is driven by chemokines. Additionally, PECAM-1 (or platelet endothelial cell adhesion molecule-1) coordinates the movement of white blood cells. As well as breaking through the cell wall, the white blood cells must get through the basement membrane. This is done by the secretion of collagenases (enzymes that break down collagen). ChemotaxisChemotaxis is the movement of white blood cells in the extracellular fluid towards the target (the site of injury). This happens along a chemical gradient (higher amount of molecules vs. lower amount of molecules), and the following products can induce chemotaxis:
- Bacterial products
- Cytokines, especially chemokines
- Parts of the complement system
- Products of metabolism associated with arachidonic acid (AA).
Formation of Transudates and Exudates
Under normal circumstances, both the hydrostatic pressure (the pressure from within the vessels to the outside) and the colloid osmotic pressure (the pressure from outside the vessels pressing inside) is always equalised. During the inflammatory process, transduates and exudates are formed.
Transudates are formed during the early phase of inflammation and it consists of fluid with very little protein. The pressure toward the outside increases and the pressure toward the inside of the vessels decrease, thereby forcing (clear) fluid out and leading to oedema (swelling).
Exudates are formed during inflammation because of the increased pore sizes within the vessels. Unlike transudates, exudates are rich in proteins and can appear yellow when extracted.
How is inflammation detected within the laboratory setting?
Inflammation is detected within the lab via examining the different acute phase reaction proteins. There are two categories of acute phase reaction proteins, known as positive acute phase proteins and negative acute phase proteins, and several proteins fall under each category. The main type of protein to look at is known as C-reactive protein or CRP.
What are the positive and negative phase proteins?
The positive acute phase proteins increase in quantity when inflammation occurs, and negative acute phase proteins decrease in quantity. The functions of each of these proteins can be seen in the table alongside:
- C-reactive protein
- Complement proteins
Together, these proteins help to repair and protect the body, clean up after infection by use of phagocytic (digesting) cells, and freeing of amino acids.