MHC class I-related neonatal Fc receptor for IgG is functionally expressed in monocytes, intestinal macrophages, and dendritic cells.
The neonatal Fc receptor (FcRn) for IgG, an MHC class I-related molecule, functions to transport IgG across polarized epithelial cells and protect IgG from degradation. However, little is known about whether FcRn is functionally expressed in immune cells. We show here that FcRn mRNA was identifiable in human monocytes, macrophages, and dendritic cells. FcRn heavy chain was detectable as a 45-kDa protein in monocytic U937 and THP-1 cells and in purified human intestinal macrophages, peripheral blood monocytes, and dendritic cells by Western blot analysis. FcRn colocalized in vivo with macrosialin (CD68) and Ncl-Macro, two macrophage markers, in the lamina propria of human small intestine. The heavy chain of FcRn was associated with the beta(2)-microglobulin (beta(2)m) light chain in U937 and THP-1 cells. FcRn bound human IgG at pH 6.0, but not at pH 7.5. This binding could be inhibited by human IgG Fc, but not Fab. FcRn could be detected on the cell surface of activated, but not resting, THP-1 cells. Furthermore, FcRn was uniformly present intracellularly in all blood monocytes and intestinal macrophages. FcRn was detectable on the cell surface of a significant fraction of monocytes at lower levels and on a small subset of tissue macrophages that expressed high levels of FcRn on the cell surface. These data show that FcRn is functionally expressed and its cellular distribution is regulated in monocytes, macrophages, and dendritic cells, suggesting that it may confer novel IgG binding functions upon these cell types relative to typical Fc gamma Rs: Fc gamma RI, Fc gamma RII, and Fc gamma RIII.
Zhu
X
X
Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Meng
G
G
Dickinson
B L
BL
Li
X
X
Mizoguchi
E
E
Miao
L
L
Wang
Y
Y
Robert
C
C
Wu
B
B
Smith
P D
PD
Lencer
W I
WI
Blumberg
R S
RS
D000328:Adult; D000918:Antibody Specificity / Q000235:genetics; D015415:Biomarkers; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D006680:HLA Antigens / Q000502:physiology*; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007141:Immunoglobulin Fc Fragments / Q000502:physiology; D007074:Immunoglobulin G / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D007231:Infant, Newborn; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D019169:Jurkat Cells; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D009928:Organ Specificity / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000235:genetics; D011961:Receptors, Fc / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D001613:beta 2-Microglobulin / Q000378:metabolism
D015415:Biomarkers; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D011961:Receptors, Fc; D017452:Receptors, IgG; D001613:beta 2-Microglobulin; C100688:Fc receptor, neonatal