Anaphylatoxin

Anaphylatoxins are small proteins that are produced as part of the immune system's response to a threat. They are known to play a pivotal role in the body's defense mechanism by triggering inflammation, attracting white blood cells to the site of infection or injury, and increasing the permeability of blood vessels to allow immune cells to more easily reach the affected area. Anaphylatoxins are part of the complement system, a complex series of enzyme cascades designed to fight off pathogens and clear them from the body.

Production and Activation

Anaphylatoxins are generated through the activation of the complement system, specifically during the cleavage of complement proteins C3, C4, and C5. The cleavage of these proteins results in the formation of anaphylatoxins C3a, C4a, and C5a. The activation of the complement system can occur through one of three pathways: the classical pathway, which is triggered by antibody-antigen complexes; the lectin pathway, which is initiated by the binding of mannose-binding lectin to pathogen surfaces; and the alternative pathway, which can be activated directly on pathogen surfaces in the absence of antibodies.

Functions

The primary functions of anaphylatoxins include:

• Inducing Inflammation: Anaphylatoxins can increase vascular permeability, allowing more immune cells to reach the site of infection or injury.
• Chemotaxis: They act as chemokines, substances that attract immune cells such as neutrophils and monocytes to the site where they are needed.
• Activation of Immune Cells: Anaphylatoxins can stimulate immune cells, enhancing their ability to fight off pathogens.

C5a is considered the most potent of the anaphylatoxins, with strong chemotactic properties and the ability to activate immune cells. C3a and C4a are also important but are generally less potent than C5a.

Regulation

The activity of anaphylatoxins is tightly regulated by the body to prevent excessive inflammation, which can lead to tissue damage. Various enzymes and receptors on the surface of immune cells act to degrade anaphylatoxins or inhibit their functions. For example, the enzyme carboxypeptidase N removes the C-terminal arginine from anaphylatoxins, reducing their activity.

Clinical Significance

Anaphylatoxins have been implicated in a variety of diseases where inflammation plays a key role, such as asthma, rheumatoid arthritis, and sepsis. Their role in these diseases makes them a potential target for therapeutic intervention. Drugs that can inhibit the production or function of anaphylatoxins may be beneficial in treating inflammatory conditions.

See Also

• Complement system
• Inflammation
• Immune system
• Chemokine