Complement C3a

Complement C3a, a small 9 kDa peptide, has 77 amino acids and made up of four anti-parallel helical structures that are trapped by three disulfide bridges. C3a is an important chemotactic mediator in the immune system, and the C3a/C3aR pathway plays crucial anti-inflammatory and proinflammatory roles in different cells and diseases. Generally, C3a/C3aR participates in the response of the immune system in three ways, including (1) activate dendritic cells (DCs), acting on resident innate immune cells to up-regulate or down-regulate different cytokines, and regulate T cell signaling between lymphocytes and antigen presenting cells (APCs).

Fig.1 Double edged sword of C3a/C3aR. (Gao, 2020)

Besides, C3a also has anti-inflammatory effects in pathogens, such as neutrophils in the bone marrow reservoir, bacteria/fungi, as well as natural killer (NK) cells. What’s more, although there is a high expression of functional C3aR on the neutrophil cell membrane, C3a does not stimulate neutrophil degranulation to activate inflammatory response. Also, through directly inhibiting neutrophil mobilizing factors (e.g., G-CSF), C3a can suppress the migration of neutrophils from the bone marrow into the circulation. Typically, in healthy individuals, the plasma concentration of C3a is 119 ng/mL, and it is generated by the degradation of C3 in the alternative pathway. But in different researches, owning to protocol and sample characteristics, the C3a concentration varies widely, from 20 to 156 ng/mL.

Reference

1. Gao, S., et al. The complement C3a and C3a receptor pathway in kidney diseases. Frontiers in Immunology. 2020, 11.