title: FcRn: an IgG receptor on phagocytes with a novel role in phagocytosis.
abstract: Here, we report that the MHC class I-related neonatal Fc receptor (FcRn) is expressed within azurophilic and specific granules of neutrophils and relocates to phagolysosomes on phagocytosis of IgG-opsonized bacteria. We found FcRn to enhance phagocytosis in a pH-dependent manner which was independent of IgG recycling. IgG-opsonized bacteria were inefficiently phagocytosed by neutrophils from beta2M knock-out or FcRn alpha-chain knock-out mice, which both lack expression of FcRn. Similarly, low phagocytic activity was also observed with mutated IgG (H435A), which is incapable of binding to FcRn, while retaining normal binding to classical leukocyte Fcgamma receptors. Finally, a TAT peptide representing intracellular endocytosis and transport motifs within FcRn strongly inhibited IgG-mediated phagocytosis. These findings support a novel concept in which FcRn fulfills a major role in IgG-mediated phagocytosis.
authors.affiliation: Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. G.Vidarsson@sanquin.nl
authors.forename: Gestur
authors.initials: G
authors.lastname: Vidarsson
authors.forename: Annette M
authors.initials: AM
authors.lastname: Stemerding
authors.forename: Nigel M
authors.initials: NM
authors.lastname: Stapleton
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Spliethoff
authors.forename: Hans
authors.initials: H
authors.lastname: Janssen
authors.forename: Frank E
authors.initials: FE
authors.lastname: Rebers
authors.forename: Masja
authors.initials: M
authors.lastname: de Haas
authors.forename: Jan G
authors.initials: JG
authors.lastname: van de Winkel
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology; D002451:Cell Compartmentation; D002478:Cells, Cultured; D015696:Gene Products, tat / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009504:Neutrophils / Q000502:physiology*; D010586:Phagocytes / Q000502:physiology; D010587:Phagocytosis; D011961:Receptors, Fc / Q000378:metabolism / Q000502:physiology*
chemical_list: D015696:Gene Products, tat; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; C100688:Fc receptor, neonatal