FcRn-mediated transcytosis of immunoglobulin G in human renal proximal tubular epithelial cells.
In the kidney, proteins filtered through glomeruli are reabsorbed by endocytosis along the proximal tubules to avoid renal loss of large amounts of proteins. Recently, neonatal Fc receptor (FcRn), which is involved in the transport of IgG across several epithelial and endothelial cells, was reported to be expressed in renal proximal tubular epithelial cells (RPTECs). However, there has been no direct evidence for receptor-mediated endocytosis of IgG in human RPTECs. To explore physiological roles of FcRn in the proximal tubules, we used the human RPTECs to examine IgG transport. FcRn was expressed in RPTECs and physically associated with beta(2)-microglobulin, preserving the capacity of specific pH-dependent IgG binding. Human IgG was bound to the cell surface of RPTECs in a pH-dependent manner. The human IgG transport assay revealed that receptor-mediated transepithelial transport of intact IgG in RPTECs is bidirectional and that it requires the formation of acidified intracellular compartments. With the use of double immunofluorescence, the internalized human IgG was marked in cytoplasm of RPTECs and colocalized with FcRn. These data define the mechanisms of FcRn-associated IgG transport in RPTEC monolayers. It was suggested that the intact pathway for human IgG transepithelial transport may avoid lysosomal degradation of IgG.
Kobayashi
Noriyoshi
N
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Suzuki
Yusuke
Y
Tsuge
Toshinao
T
Okumura
Ko
K
Ra
Chisei
C
Tomino
Yasuhiko
Y
D001692:Biological Transport / Q000276:immunology; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D015395:Histocompatibility Antigens Class I; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG / Q000235:genetics; D001613:beta 2-Microglobulin / Q000235:genetics
D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011961:Receptors, Fc; D017452:Receptors, IgG; D001613:beta 2-Microglobulin; C100688:Fc receptor, neonatal