Complement C5a Receptor 1 (C5aR1)

C5aR1, also known as CD88 (cluster of differentiation 88), is a seven-transmembrane protein expressed on myeloid, endothelial, epithelial, and smooth muscle cells, belonging to the family of G-protein-coupled receptors (GPCRs). It is a receptor for C5a, the most potent chemotactic and inflammatory peptide. Structurally, there have at least two sites on the receptor interacting with the ligand C5a, one is on the extracellular N-terminus and the other is in the transmembrane region. Functionally, C5aR1 activation is involved in the stimulation of chemotaxis, granule enzyme release, intracellular calcium release, and the production of superoxide anion. C5aR1 also serves as a component of the classical pathway of the complement cascade, participating in the host-defense responses. Furthermore, C5aR1 may be a component of the membrane attack complex, involved in tissue injury associated with ischemia or sepsis.

Because of the crucial role in the regulation of inflammatory responses, C5aR1 signaling pathway has been revealed an association with some inflammatory diseases such as cancer. C5aR1 has been found in a variety of tumor cell types such as colon, esophagus, stomach, bile duct, liver, and breast. High levels of C5aR1 in human tumor cells are greatly associated with poor prognosis, such as shorter recurrence-free survival, overall survival, and bone metastasis. Blockage of C5aR1 can impair tumor cell growth and metastasis. Furthermore, C5aR1 signaling pathway has been also indicated a key role in acute lung injury induced by influenza virus infection. C5a-C5aR1 inhibition can suppress the viral replication in lung tissue, thereby alleviating the symptoms of acute lung injury.

Fig.1 Structure and function of complement C5a receptors. (Pandey, 2020)

Reference

1. Pandey, S.; et al. Emerging Insights into the Structure and Function of Complement C5a Receptors. Trends in Biochemical Sciences. 2020, (45)8: 693-705.