Renal FcRn reclaims albumin but facilitates elimination of IgG.
The widely distributed neonatal Fc receptor (FcRn) contributes to maintaining serum levels of albumin and IgG in adults. In the kidney, FcRn is expressed on the podocytes and the brush border of the proximal tubular epithelium. Here, we evaluated the role of renal FcRn in albumin and IgG metabolism. Compared with wild-type controls, FcRn(-/-) mice had a lower t((1/2)) for albumin (28.7 versus 39.9 h) and IgG (29.5 versus 66.1 h). Renal loss of albumin could account for the former, suggested by the progressive development of hypoalbuminemia in wild-type mice transplanted with FcRn-deficient kidneys. Furthermore, serum albumin levels returned to normal in FcRn(-/-) recipients of wild-type kidneys after removing the native FcRn-deficient kidneys. In contrast, renal loss could not account for the enhanced elimination of IgG in FcRn(-/-) mice. These mice had minimal urinary excretion of native and labeled IgG, which increased to wild-type levels in FcRn(-/-) recipients of a single FcRn-sufficient kidney (t((1/2)) of IgG was 21.7 h). Taken together, these data suggest that renal FcRn reclaims albumin, thereby maintaining the serum concentration of albumin, but facilitates the loss of IgG from plasma protein pools.
Sarav
Menaka
M
Section of Nephrology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Wang
Ying
Y
Hack
Bradley K
BK
Chang
Anthony
A
Jensen
Mark
M
Bao
Lihua
L
Quigg
Richard J
RJ
D000419:Albuminuria / Q000378:metabolism; D000818:Animals; D005260:Female; D005456:Fluorescent Dyes; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D007074:Immunoglobulin G / Q000097:blood / Q000652:urine*; D007668:Kidney / Q000378:metabolism*; D016030:Kidney Transplantation; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008871:Microvilli / Q000378:metabolism; D008954:Models, Biological; D009930:Organic Chemicals; D050199:Podocytes / Q000378:metabolism; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D012709:Serum Albumin / Q000493:pharmacokinetics*
C417664:Alexa594; D005456:Fluorescent Dyes; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D009930:Organic Chemicals; D011961:Receptors, Fc; D012709:Serum Albumin; C100688:Fc receptor, neonatal