Functional expression of the MHC class I-related receptor, FcRn, in endothelial cells of mice

Abstract

Our recent data indicate that the MHC class I-related receptor, FcRn, plays a role in regulating serum IgG levels, in addition to its known role in transferring IgG from mother to young. In the current study, the distribution of FcRn in adult mice has been investigated using several approaches. First, tissue distribution of anti-FcRn F(ab')2, murine IgG1 and recombinant, IgG1-derived Fc-hinge fragments has been analyzed, and these FcRn binding proteins localize predominantly in skin and muscle with lesser amounts in liver and adipose tissue. Second, histochemical analyses of muscle and liver with anti-FcRn F(ab')2 indicate that FcRn is expressed in the endothelium of small arterioles and capillaries, but not in larger vessels such as the central vein and portal vasculature. Third, immunoprecipitation and immunofluorescence studies of cultured murine endothelial cells show that functional FcRn is expressed in these cells, and is located within vesicular structures in the cytosol and not on the membrane. Taken together the data demonstrate that FcRn is expressed in functionally active form in endothelial cells, indicating that these cells are a possible site at which serum IgG homeostasis is maintained.

Neonatal FcR Expression in Bone Marrow-Derived Cells Functions to Protect Serum IgG from Catabolism

“…Because the vascular endothelium of skin and skeletal muscle are proposed to be the sites at which FcRn protects serum IgG from degradation, we first examined these tissues (15). Consistent with previous reports, we found that FcRn was expressed at high levels in the vasculature of these organs (Fig.…”

“…To protect serum IgG from catabolism, FcRn is predicted to function at sites that have a large contact area with the blood such as the vascular endothelium of the skin and skeletal muscle (15). In fact, FcRn has been shown to be highly expressed in a variety of different endothelial beds.…”

“…In fact, FcRn has been shown to be highly expressed in a variety of different endothelial beds. A significant body of work has established that FcRn, expressed in endothelial cells, intercepts internalized IgG and returns it to the circulation thus protecting it from lysosomal degradation (13,(15)(16)(17)(18). Although expression of the homeostatic IgG receptor in the vascular endothelium makes logical sense, FcRn is also expressed at other sites in adult animals.…”

“…Although FcRn expression has been reported in hepatocytes (19) and hepatic sinusoidal cells (15), expression in other organs of the reticuloendothelial system were not examined. We confirmed strong FcRn staining in the sinusoidal cells of the liver (Fig.…”

Kinetics of FcRn-mediated recycling of IgG and albumin in human: Pathophysiology and therapeutic implications using a simplified mechanism-based model

“…The full model (Fig. 1A) features a functional catabolic and recycling site within the vascular compartment consisting of endosome-rich endothelium [24] into which plasma IgG is constitutively pinocytosed by a fluid-phase endocytic process at a fractional uptake rate (k up ), which is FcRn-independent since FcRn binding takes place after acidic sorting endosomes are formed [25], unlike cell-surface receptor-mediated uptake of LDL or transferrin. While pinocytosis/exocytosis is potentially bidirectional, k up is a fractional rate of "net" movement (thus smaller in magnitude than the 'real' unidirectional uptake rate) from the plasma into the sorting endosomes where IgG binds FcRn according to its binding affinity (equilibrium binding constant; K D ) in an acidic endosomal environment [25].…”