The inverse relationship between serum albumin concentration and its half-life suggested to early workers that albumin would be protected from a catabolic fate by a receptor-mediated mechanism much like that proposed for IgG. We show here that albumin binds FcRn in a pH dependent fashion, that the lifespan of albumin is shortened in FcRn-deficient mice, and that the plasma albumin concentration of FcRn-deficient mice is less than half that of wild-type mice. These results affirm the hypothesis that the major histocompatibility complex–related Fc receptor protects albumin from degradation just as it does IgG, prolonging the half-lives of both.

A model was developed that characterized the maturation and growth of the renal function parameters (RFPs) glomerular filtration rate (GF), active tubular secretion (AS), and renal plasma flow (Q R ).Published RFP values were obtained from 63 healthy children between the ages of 2 days and 12 years. Maturation over time was assumed to be exponential from an immature (RFP im ) to a mature (RFP ma ) level; for growth, RFP im and RFP ma were assumed to follow the allometric equation: RFP (age, W) = aW b e -kmat*age + cW b (1 -e -kmat*age ),

The nonclassical MHC class-I molecule, FcRn, salvages both IgG and albumin from degradation. Here we introduce a mechanism-based kinetic model for human to quantify FcRn-mediated recycling of both ligands based on saturable kinetics and data from the literature using easily measurable plasma concentrations rather than unmeasurable endosomal concentrations. The FcRn-mediated fractional recycling rates of IgG and albumin were 142% and 44% of their fractional catabolic rates, respectively. Clearly, FcRn-mediated recycling is a major contributor to the high endogenous concentrations of these two important plasma proteins. While familial hypercatabolic hypoproteinemia is caused by complete FcRn deficiency, the hypercatabolic IgG deficiency of myotonic dystrophy could be explained, based on the kinetic analyses, by a normal number of FcRn with lowered affinity for IgG but normal affinity for albumin. A simulation study demonstrates that the plasma concentrations of IgG and albumin could be dynamically controlled by both FcRn-related and -unrelated parameters.

It is now understood that the nonclassical major histocompatibility complex-I molecule FcRn binds albumin and retrieves it from an intracellular degradative fate. Whether FcRn in the liver modulates albumin turnover through effects on biosynthesis and production is not known. Thus we quantified the appearance of biosynthetically labeled albumin in plasma after an intravenous bolus injection of [ 3 H]leucine in FcRndeficient mice. The production rates for both albumin (FcRn substrate) and transferrin (nonsubstrate) are increased by ϳ20% in FcRndeficient mice compared with normal mice, likely compensating for the lowered plasma oncotic pressure caused by hypoalbuminemia in FcRn-deficient mice. Determining the magnitude of FcRn-mediated effects on albumin turnover, we then measured the steady-state plasma concentrations of biosynthetically labeled albumin and transferrin during [ 3 H]leucine infusion. The concentration of albumin was ϳ40% lower in FcRn-deficient mice compared with normal mice. Furthermore, the ϳ40% lower plasma albumin concentration in FcRndeficient mice along with the ϳ20% increase in albumin production indicate, by the mass-balance equation, that albumin degradation in FcRn-deficient mice is twice that of normal mice. These studies of biosynthetically labeled, and thus native, albumin support our previous finding that FcRn protects albumin from degradation. Permitting quantification of the magnitude of FcRn-mediated recycling, they further indicate that FcRn has extraordinary capacity: the amount of albumin saved from degradation by FcRn-mediated recycling is the same as that produced by the liver. production; clearance; steady-state; kinetics; Fc receptor ALBUMIN and IGG, the two most abundant proteins in plasma, bind at low pH with high affinity to independent sites on the major histocompatibility complex-related Fc receptor (FcRn). Situated in acidic endosomes of virtually all nucleated cells, FcRn binds both ligands after they have been constitutively endocytosed, shunting them back to the pH-neutral cell surface for continuing circulation, thereby rescuing them from their usual lysosomal degradation fate. FcRn-deficient mice that lack such an FcRn-mediated recycling process (13) show shorter half-lives and lower steady-state plasma concentrations (Css) of both proteins than do normal mice (8).From our earlier measurements of radioiodinated albumin clearance (CL) and endogenous Css, we had inferred that the production rate (Rp) of albumin, using the mass-balance equation (Rp ϭ CL ϫ Css), was lower in the FcRn knockout (KO) strain compared with the wild-type (WT) strain (8). However, we acknowledged the estimations of CL for radioiodinated albumin to be only qualitative, for such measurements for albumin have historically been fraught with imprecision due to structural and/or functional alterations induced by purification and iodination (32). In fact, we had anticipated finding a greater albumin Rp in KO mice, for it had long been known that hypoalbuminemia induces an upregulation of the synth...

Cardiac output, blood flow distribution and regional perfusion were determined in free-swimming rainbow trout acclimated to 6, 12 and ls"C, using the indicator dilution and microsphere methods. Cardiac output (ml min-kg-I ) increased linearly with increasing temperature, while circulation time decreased. Blood flow distribution (% of cardiac output) to the spleen, liver, kidney, gall bladder and gastro-intestinal tract was significantly reduced at 18" C relative to 6" Cacclimated fish. White muscle received the largest fraction of cardiac output, and blood flow distribution to white muscle increased significantly with increasing acclimation temperature.Blood perfusion (ml h-I g-') of various organs and red muscle was not influenced by acclimation temperature, while white muscle perfusion increased with increasing temperature. These results demonstrate physiological adaptation of the cardiovascular system of rainbow trout to changes in acclimation temperature.