FcγRIIa expression with FcγRI results in C-reactive protein- and IgG-mediated phagocytosis

C‐reactive protein (CRP) is a pattern‐recognition molecule, which can bind to phosphorylcholine and certain phosphorylated carbohydrates found on the surface of a number of microorganisms. CRP has been shown recently to bind human Fc receptor for immunoglobulin G (IgG; FcγR)I and mediate phagocytosis and signaling through the γ‐chain. To date, binding of monomeric CRP to FcγRII has been contentious. We demonstrate that erythrocytes opsonized with CRP bind FcγRIIa‐transfected COS‐7 cells. In addition, we demonstrate that FcγRI can use FcγRIIa R131 and H131 to phagocytose erythrocytes coated with IgG or purified or recombinant CRP in the absence of the γ‐chain. COS‐7 cells expressing FcγRIIa or FcγRI alone did not phagocytose opsonized erythrocytes. Such phagocytosis required the cytoplasmic domain of FcγRIIa, as mutation of tyrosine at position 205 and truncation of the cytoplasmic domain from the end of the transmembrane region (position 206), resulting in the loss of the immunoreceptor tyrosine activatory motif, abrogated phagocytosis. FcγRIIa R131 was more efficient than FcγRIIa H131 at mediating CRP‐dependent phagocytosis.