Figure 1.

Illustration of transport of the three major plasma proteins and targeted anti-transferrin receptor antibodies within brain capillary endothelial cells (BECs). (A) Albumin and non-immune IgG enter the BEC non-specifically by fluid-phase uptake. They may undergo release from the BEC at the abluminal side, although the quantitative evidence is scarce and clearly shows that this mean for entry of albumin and non-immune IgG to the brain is negligible. (B) Similarly, the transcytotic transport of iron-containing (holo-transferrin) is also negligible and opposed by the release of iron from transferrin due to the lower pH of the endocytosis vesicle. Transport through the BECs may occur to a higher extent in the developing brain where transferrin receptor expression by BECs is far-fold higher than in the adult brain (see body text). (C) Transport of high-affine IgG targeted to the transferrin receptor. Transport of this antibody through BECs is negligible. (D) Transport of low-affine IgG targeted to the transferrin receptor. Transport of this antibody through BECs is enabled by the detachment of the antibody from the transferrin receptor in late endosomes, which enables this antibody to undergo transport into the brain. Modified from [15].