RAGE binds C1q and enhances C1q-mediated phagocytosis

RAGE, the multiligand receptor of the immunoglobulin superfamily of cell surface molecules, is implicated in innate and adaptive immunity. Complement component C1q serves roles in complement activation and antibody-independent opsonization. Using soluble forms of RAGE (sRAGE) and RAGE-expressing cells, we determined that RAGE is a native C1q globular domain receptor. Direct C1q–sRAGE interaction was demonstrated with surface plasmon resonance (SPR), with minimum Kd 5.6 μM, and stronger binding affinity seen in ELISA-like experiments involving multivalent binding. Pull-down experiments suggested formation of a receptor complex of RAGE and Mac-1 to further enhance affinity for C1q. C1q induced U937 cell adhesion and phagocytosis was inhibited by antibodies to RAGE or Mac-1. These data link C1q and RAGE to the recruitment of leukocytes and phagocytosis of C1q-coated material.

► RAGE is a newly identified, native C1q globular domain receptor. ► A receptor complex of RAGE and Mac-1 could be formed with enhanced affinity for C1q. ► C1q-induced cell adhesion and phagocytosis was inhibited by RAGE or Mac-1 antibodies. ► RAGE is linked to leukocyte recruitment and phagocytosis of C1q-coated material.