Podocytes use FcRn to clear IgG from the glomerular basement membrane

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. Keywords: Unique cell type expression analysis Total RNA for genechip analysis was derived from two sources: 1) Primary mouse podocytes isolated by FACS sorting of collagenase digested glomeruli 2) In vitro differentiated conditionally immortalized mouse podocyte cell line. After obtaining genechip data, the expression of various IgG and albumin receptors was queried in the genechip data and then confirmed by RT-PCR.