Podocytes use FcRn to clear IgG from the glomerular basement membrane.
Document Type
Article
Publication Date
2008
Keywords
Cell-Line, Female, Glomerular-Basement-Membrane, Histocompatibility-Antigens-Class-I, Immunoglobulin-G, Mice-Knockout, Nephritis, Podocytes, Protein-Transport, Receptors-Fc, Sensitivity-and-Specificity, Serum
First Page
967
Last Page
972
JAX Source
Proc Natl Acad Sci U S A 2008 Jan; 105(3):967-72.
Abstract
The glomerular filtration barrier prevents large serum proteins from being lost into the urine. It is not known, however, why the filter does not routinely clog with large proteins that enter the glomerular basement membrane (GBM). Here, we provide evidence that an active transport mechanism exists to remove immunoglobulins that accumulate at the filtration barrier. We found that FcRn, an IgG and albumin transport receptor, is expressed in podocytes and functions to internalize IgG from the GBM. Mice lacking FcRn accumulated IgG in the GBM as they aged, and tracer studies showed delayed clearance of IgG from the kidneys of FcRn-deficient mice. Supporting a role for this pathway in disease, saturating the clearance mechanism potentiated the pathogenicity of nephrotoxic sera. These studies support the idea that podocytes play an active role in removing proteins from the GBM and suggest that genetic or acquired impairment of the clearance machinery is likely to be a common mechanism promoting glomerular diseases.
Recommended Citation
Akilesh S,
Huber TB,
Wu H,
Wang G,
Hartleben B,
Kopp JB,
Miner JH,
Roopenian DC,
Unanue ER,
Shaw AS.
Podocytes use FcRn to clear IgG from the glomerular basement membrane. Proc Natl Acad Sci U S A 2008 Jan; 105(3):967-72.