autologous blood and marrow transplantation - Blog Science ...

5h P
11-
V
Junghans 669
o I 1 1 1 1
0 10 20 30 40
Y-globulin concentration (mg/ml)
Figure 2. Relation of half-life to serum concentration of y-globulin in mice. Simulation (so
line) according to receptor model of Brambell with a=0.34, b=2.5. From Brambell et a
with permission.
IgG binding by a pH-dependent mechanism: after nonspecific bulk endocytosis, IgG
Fc binds to FcRB in the acidic environment (pH 6) of the endosome, the IgG
attached to the receptor is directed away from the lysosomes via an alternate
pathway, and then it is released in the physiologic neutrality (pH 7.4) of extracellular
fluids after return to the cell surface. The overall process is summarized in Fig. 3,
including the effect of IgG concentration on receptor saturation.
The receptor itself was purified first by Rodewald and Krahenbuhl 6
and later
cloned by Simister and Mostov. 7
This cloned receptor was initially termed FcRn for
neonatal rat intestine, the tissue from which cloning was first performed. It is notable
that many animals, including humans, have little or no neonatal IgG transmission,
with the major expression of this transport receptor occurring antenatally instead.
Nevertheless, the term FcRn has been broadly applied to the transmission function
of this receptor. It was subsequently confirmed that the same protein also mediates
the IgG protection function (FcRp): animals knocked-out for the receptor showed
accelerated IgG catabolism 8
" 10
(Fig. 4) as well as loss of perinatal transport. 11
In
adult animals, the dominant expression is, in fact, as protection receptor (FcRp),
making IgG the longest-surviving of all plasma proteins. Although an early report
suggested that the FcRB might be involved in transport of IgG from blood to bile,
its action in liver appears to be solely as FcRp, paralleling the basal endocytic