Mechanism of hypoalbuminemia in rodents.
Normal albumin loss from the plasma is thought to be minimized by a number of mechanisms, including charge repulsion with the capillary wall and an intracellular rescue pathway involving the major histocompatibility complex-related Fc receptor (FcRn)-mediated mechanism. This study investigates how these factors may influence the mechanism of hypoalbuminemia. Hypoalbuminemia in rats was induced by treatment with puromycin aminonucleoside (PA). To test the effects of PA on capillary wall permeability, plasma elimination rates were determined for tritium-labeled tracers of different-sized Ficolls, negatively charged Ficolls, and (14)C-labeled tracer of albumin in control and PA-treated Sprague-Dawley rats. Urinary excretion and tissue uptake were also measured. Hypoalbuminemia was also examined in two strains of FcRn-deficient mice: beta(2)-microglobulin (beta(2)M) knockout (KO) mice and FcRn alpha-chain KO mice. The excretion rates of albumin and albumin-derived fragments were measured. PA-induced hypoalbuminemia was associated with a 2.5-fold increase in the plasma elimination rate of albumin. This increase could be completely accounted for by the increase in urinary albumin excretion. Changes in the permeability of the capillary wall were not apparent, inasmuch as there was no comparable increase in the plasma elimination rate of 36- to 85-A Ficoll or negatively charged 50- to 80-A Ficoll. In contrast, hypoalbuminemic states in beta(2)M and FcRn KO mice were associated with decreases in excretion of albumin and albumin-derived fragments. This demonstrates that the mechanism of hypoalbuminemia consists of at least two distinct forms: one specifically associated with the renal handling of albumin and the other mediated by systemic processes.
Koltun
Maria
M
Dept. of Biochemistry and Molecular Biology, Monash University, Wellington Road, Clayton, Victoria 3800, Australia.
Nikolovski
Julijana
J
Strong
Kimberley
K
Nikolic-Paterson
David
D
Comper
Wayne D
WD
D000418:Albumins / Q000493:pharmacokinetics*; D000419:Albuminuria / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D000964:Antimetabolites, Antineoplastic; D002199:Capillary Permeability / Q000502:physiology; D002250:Carbon Radioisotopes; D005362:Ficoll / Q000493:pharmacokinetics; D034141:Hypoalbuminemia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011692:Puromycin Aminonucleoside; D051381:Rats; D017207:Rats, Sprague-Dawley; D011961:Receptors, Fc / Q000235:genetics; D014316:Tritium; D001613:beta 2-Microglobulin / Q000235:genetics
D000418:Albumins; D000964:Antimetabolites, Antineoplastic; D002250:Carbon Radioisotopes; D011961:Receptors, Fc; D001613:beta 2-Microglobulin; D014316:Tritium; D005362:Ficoll; D011692:Puromycin Aminonucleoside