Chemotaxis

To understand the general principles involved in inflammation, it is not necessary to consider chemotaxis in detail. Chemotaxis is, however, a process which will be of increasing importance to us. Since a detailed consideration of chemotaxis is not necessary for an explanation of inflammation, I have chosen to treat it under its own, distinct heading. It may be preferable for some of you to come back to this after finishing the the discussion of inflammation. Nevertheless, understanding chemotaxis will be important and it is convenient to treat it here, so as to give the fullest explanation of inflammation.

In the case of neutrophils (to take an example), chemotaxis is achieved by the formation of pseudopods. These are temporary extensions of the cell, which roughly resemble feet. When a cell such as a neutrophil detects a concentration gradient of a chemotactic factor, it will physically stretch towards it. That is to say that, where there exists a high concentration of chemotactic factors, the cell will project pseudopods towards that concentration. In this way, the cell directs its movement along the concentration gradient. Pseudopods may be extended and contracted such that they can accurately follow the concentration gradient and respond to any changes. Some examples of these chemotactic factors which are followed by neutrophils are interleukin-8 (IL-8), complement component 5a (C5a), N-Formylmethionine leucyl-phenylalanine (fMLP) and leukotriene B4.

At this point, I am afraid that I'm going to have to become rather vague, because the mechanism by which these pseudopods are created is not fully understood. Nevertheless, we know that the formation of these pseudopods is effected by receptors on the surface of the cell. These receptors are specialised proteins, which bind with the relevant chemotactic factor for that cell. It is believed that this leads to the creation of a gradient of PIP₃ within the cell.

PIP₃ is a phospholipid whose full, unabbreviated name is phosphatidylinositol (3,4,5)-triphosphate and it looks like this:

Figure 1.1: The structural formula of PIP₃. (Image courtesy of "Louisajb," via Wikipedia)

When a chemotactic factor binds to a cell surface receptor, the reaction will bring about a conformational change in the receptor. The receptor will change its shape. In the case of neutrophils, this change leads to the production of PIP₃, which is, naturally, concentrated around the receptor. PIP₃ is involved in a signalling pathway, which is where a series of chemical reactions - beginning with a ligand (literally any chemical which binds to another to form a more complex chemical) binding to a receptor - form the required components to produce a desired effect within the cell. For more information and a detailed example see cell signalling. Suffice it to say, for the time being, that the signalling pathway ultimately leads to the polymerisation of actin filaments. Actin is a protein which is used to build the pseudopods. The external concentration gradient sets up an internal PIP₃ gradient (for PIP₃ will be produced at the site of the receptors, with more PIP₃ produced where there is more of the chemotactic factor to instigate its production) which leads to heightened levels of actin filament polymerisation at that location. These actin polymers connect with the membrane of the cell forming a growth - the pseudopod. Actin filaments can be readily polymerised and depolymerised, allowing for suitably rapid construction and deconstruction of the pseudopods, which allows the neutrophil to follow the concentration gradient.