FcRn: an IgG receptor on phagocytes with a novel role in phagocytosis.
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.
Vidarsson
Gestur
G
Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. G.Vidarsson@sanquin.nl
Stemerding
Annette M
AM
Stapleton
Nigel M
NM
Spliethoff
Suzanne E
SE
Janssen
Hans
H
Rebers
Frank E
FE
de Haas
Masja
M
van de Winkel
Jan G
JG
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*
D015696:Gene Products, tat; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; C100688:Fc receptor, neonatal