| First Author | Saggu G | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 5058 |
| PubMed ID | 30498196 | Mgi Jnum | J:267766 |
| Mgi Id | MGI:6267875 | Doi | 10.1038/s41467-018-07506-1 |
| Citation | Saggu G, et al. (2018) Cis interaction between sialylated FcgammaRIIA and the alphaI-domain of Mac-1 limits antibody-mediated neutrophil recruitment. Nat Commun 9(1):5058 |
| abstractText | 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 FcgammaRIIA in cis to reduce the affinity of FcgammaRIIA for IgG and inhibit FcgammaRIIA-mediated neutrophil recruitment under flow. The Mac-1 rs1143679 lupus-risk variant reverses Mac-1 inhibition of FcgammaRIIA, as does a Mac-1 ligand and a mutation in Mac-1's ligand binding alphaI-domain. Sialylated complex glycans on FcgammaRIIA interact with the alphaI-domain via divalent cations, and this interaction is required for FcgammaRIIA inhibition by Mac-1. Human neutrophils deficient in CD18 integrins exhibit augmented FcgammaRIIA-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 FcgammaRIIA and the alphaI-domain of Mac-1 alters the threshold for IgG-mediated neutrophil recruitment. A disruption of this interaction may increase neutrophil influx in autoimmune diseases. |
