Submitted December 16, 2005
Accepted July 5, 2006
FcRn: an IgG receptor on phagocytes with a novel role in
phagocytosis
Gestur Vidarsson*, Annette M Stemerding, Nigel M Stapleton, Suzanne E Spliethoff, Hans Janssen, Frank E Rebers, Masja de Haas, and Jan G van de Winkel
Immunotherapy Laboratory, Dept of Immunology, University Medical Center, Utrecht, The Netherlands
Dept. Experimental Immunohematology, Sanquin Research, & Landsteiner Lab., University of Amsterdam
Division of Cell Biology, Netherlands Cancer Institute, Amsterdam, The Netherlands
* Corresponding author; email: g.vidarsson{at}sanquin.nl.
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 upon 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
2M knock-out or FcRn
-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 Fc
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.