Neonatal Fc receptors discriminates and monitors the pathway of native and modified immunoglobulin G in placental endothelial cells

Human Immunology
L RădulescuM Simionescu

Abstract

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.

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Citations

Oct 5, 2010·Journal of Clinical Immunology·Timothy T KuoRichard S Blumberg
Jan 12, 2012·Clinical & Developmental Immunology·Patricia PalmeiraMagda Carneiro-Sampaio
Mar 20, 2009·European Journal of Obstetrics, Gynecology, and Reproductive Biology·Elisabeth SölderPaul L Debbage
Jan 7, 2014·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Christopher J BowmanSimon Chivers
Dec 7, 2013·Journal of Receptor and Signal Transduction Research·Zehua TianXiaoying Zhang
Dec 11, 2021·Journal of Leukocyte Biology·Marcia Arenas-HernandezNardhy Gomez-Lopez

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