Neonatal Fc receptors discriminates and monitors the pathway of native and modified immunoglobulin G in placental endothelial cells.
In the placenta, immunoglobulin G (IgG) is selectively transported from mother to fetus by a highly regulated transcellular mechanism aimed to achieve fetal humoral immunity. We questioned the role of neonatal Fc receptors (FcRn) in the traffic of IgG in human placental endothelial cells (HPEC). Cells were cultured in a double-chamber system and further exposed to IgG or Fc or to diethylpyrocarbonate-modified IgG or Fc in which the receptor recognition domain of the molecule (CH2-CH3) was altered. We provide evidence that the native IgG/Fc probes are transcytosed or recycled by HPEC, whereas the probes with the altered receptor recognition domain (which do not bind to FcRn) massively accumulate into the endocytic/lysosomal compartments. The results indicate that FcRn distinguishes between the intact and modified IgG and control their cellular traffic: native IgG is salvaged and released out of the cells, whereas modified IgG is retained and sorted to a degradative pathway. The data advance the understanding of the basic mechanism for IgG traffic in human endothelial cells, which may be exploited for the specific transport of antibodies in various immune disorders.
Radulescu
Luminita
L
Institute of Cellular Biology and Pathology Nicolae Simionescu, 8, B. P. Hasdeu Street, Bucharest, 79691, Romania.
Antohe
Felicia
F
Jinga
Victor
V
Ghetie
Victor
V
Simionescu
Maya
M
D002478:Cells, Cultured; D004047:Diethyl Pyrocarbonate / Q000737:chemistry; D004705:Endocytosis / Q000276:immunology / Q000502:physiology; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000276:immunology* / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D008431:Maternal-Fetal Exchange / Q000276:immunology; D010920:Placenta / Q000166:cytology / Q000276:immunology*; D011247:Pregnancy; D021381:Protein Transport / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology*
D007127:Immunoglobulin Constant Regions; D007074:Immunoglobulin G; D011961:Receptors, Fc; D004047:Diethyl Pyrocarbonate