Cis interaction between sialylated Fc?RIIA and the ?I-domain of Mac-1 limits antibody-mediated neutrophil recruitment.

ABSTRACT: Vascular-deposited IgG immune complexes promote neutrophil recruitment, but how this process is regulated is still unclear. Here we show that the CD18 integrin Mac-1, in its bent state, interacts with the IgG receptor Fc?RIIA in cis to reduce the affinity of Fc?RIIA for IgG and inhibit Fc?RIIA-mediated neutrophil recruitment under flow. The Mac-1 rs1143679 lupus-risk variant reverses Mac-1 inhibition of Fc?RIIA, as does a Mac-1 ligand and a mutation in Mac-1's ligand binding ?I-domain. Sialylated complex glycans on Fc?RIIA interact with the ?I-domain via divalent cations, and this interaction is required for Fc?RIIA inhibition by Mac-1. Human neutrophils deficient in CD18 integrins exhibit augmented Fc?RIIA-dependent recruitment to IgG-coated endothelium. In mice, CD18 integrins on neutrophils dampen IgG-mediated neutrophil accumulation in the kidney. In summary, cis interaction between sialylated Fc?RIIA and the ?I-domain of Mac-1 alters the threshold for IgG-mediated neutrophil recruitment. A disruption of this interaction may increase neutrophil influx in autoimmune diseases.

SUBMITTER: Saggu G 

PROVIDER: S-EPMC6265255 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature