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Human blood-brain barrier transferrin receptor.

W M Pardridge, J Eisenberg, J Yang

Metabolism: Clinical and Experimental

|September 1, 1987

Summary

The human blood-brain barrier (BBB) transferrin receptor binds and internalizes holotransferrin, crucial for iron transport. This receptor

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Area of Science:

Neuroscience
Biochemistry
Cell Biology

Background:

The blood-brain barrier (BBB) regulates the passage of substances into the brain.
Transferrin is the primary iron transport protein in the blood.
Understanding iron transport mechanisms across the BBB is vital for brain health.

Purpose of the Study:

To characterize the binding and endocytosis kinetics of holotransferrin by human brain capillaries.
To investigate the role of the transferrin receptor in iron transport across the BBB.
To compare the BBB transferrin receptor's affinity and capacity with other BBB receptors.

Main Methods:

Isolated human brain capillaries were used as a model BBB system.
125I-human holotransferrin binding and endocytosis assays were performed.
Scatchard analysis was employed to determine receptor binding parameters.
Immunodetection using a mouse monoclonal antibody and avidin/biotin/peroxidase technique.

Main Results:

Holotransferrin binding and endocytosis were temperature-dependent and saturable.
Scatchard analysis yielded a dissociation constant (Kd) of 448 +/- 110 ng/mL and maximal binding (Ro) of 8.0 +/- 1.5 ng/mg protein.
The affinity and capacity of the BBB transferrin receptor are comparable to those for insulin and IGF receptors.
The transferrin receptor was successfully detected on human brain capillaries.

Conclusions:

These studies characterize the human BBB transferrin receptor.
The findings support the hypothesis that the transferrin receptor mediates iron transcytosis across the BBB.
This receptor system is crucial for delivering iron to the brain.

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