The innate immune system identifies pathogens by recognizing known elements. This response ultimately leads to the production of proinflammatory substances and the activation of phagocytic neutrophils and macrophages¹. Activation of the complement system is an important initial even in the response against pathogens. This system includes some thirty different proteins that act together to form a complex¹.

C5a is one of the most potent inflammatory peptides generated by complement activation. This peptide has many functions such as acting as a chemoattractant for neutrophils^2,3. C5a acts as a vasodilator^3,4 and activates the coagulation pathway^3,5 just to name a few.

C5a exerts its numerous actions by binding to C5aR and C5L2. C5aR belongs to the superfamily of G-protein coupled receptors (GPCRs). Like all members, C5aR has seven transmembrane domains, an extracellular N-terminus and an intracellular C-terminal tail. C5aR can form homodimers^6-8 or heteromer with CCR5, chemokine receptor, for example^8,9. Activation of C5aR by C5a binding causes Ca²⁺ mobilization¹⁰.

C5aR expression is detected in neutrophils, eisinophils, basophils and monocytes^3,11,12. The receptor is also expressed in lung and liver^13,14.

Blocking C5aR by peptides or organic small molecules is in the pipeline for treating chronic inflammatory disorders/diseases like arthritis, inflammatory bowel disease and lung/liver injuries⁸.