Complement C3a Products

The complement system, or complement cascade, is a part of the innate immune system that assists in defense against pathogens (1). Complement C3, also called C3 or C3 protein, is one of nine complement proteins and is the main component of the complement system which is composed of over 30 soluble and membrane-bound proteins (1). C3 is cleaved by C3 convertase into two fragments, the smaller C3a and larger C3b (1,2). Human C3a is 77 amino acids (aa) in length and has a theoretical molecular weight of ~9 kDa (2). Structurally, complement C3a consists of four anti-parallel helical structures with three disulfide bridges (2). The C3a fragment binds the G-protein coupled receptor (GPCR) C3a (C3aR) (2,3). Functionally, C3a plays an important role in regulating both adaptive immunity and innate immunity (1-3).

The C3a/C3aR pathway is often referred to as a "double-edged sword" because it has both anti-inflammatory and pro-inflammatory functions (2,3). For instance, its anti-inflammatory role includes pathogen elimination and reduced interferon-gamma (IFN-gamma) expression and cytotoxicity in natural killer cells (2). By contrast, complement C3a is an anaphylatoxin and plays a role in inflammation by prompting histamine release from mast cells and increasing permeability of the vascular system (2-4). The C3a/C3aR pathway has also been indicated in a number of diseases including Alzheimer's disease, asthma, and kidney disease (3). Patients with various kidney diseases tend to show higher levels of complement C3a in the plasma and urine (3).

References

1. Mathern, D. R., & Heeger, P. S. (2015). Molecules Great and Small: The Complement System. Clinical Journal of the American Society of Nephrology: CJASN. https://doi.org/10.2215/CJN.06230614

2. Gao, S., Cui, Z., & Zhao, M. H. (2020). The Complement C3a and C3a Receptor Pathway in Kidney Diseases. Frontiers in Immunology. https://doi.org/10.3389/fimmu.2020.01875

3. Ricklin, D., Reis, E. S., Mastellos, D. C., Gros, P., & Lambris, J. D. (2016). Complement component C3 - The "Swiss Army Knife" of innate immunity and host defense. Immunological Reviews. https://doi.org/10.1111/imr.12500

4. Haddad, A., & Wilson, A. M. (2020). Biochemistry, Complement. In StatPearls. StatPearls Publishing.