Transendothelial transport: the vesicle controversy

Area of Science:

• Physiology
• Cell Biology
• Biophysics

Background:

• The mechanisms of macromolecule transport across microvascular endothelia, specifically transcytosis versus large pore transport, remain debated.
• Inhibitors like N-ethylmaleimide (NEM) and filipin have produced conflicting data regarding their effects on endothelial transport.

Purpose of the Study:

• To resolve the controversy surrounding the relative contributions of transcytosis and passive pore transport.
• To investigate the role of active transcytosis in the movement of macromolecules like albumin and low-density lipoprotein (LDL) across endothelia.

Main Methods:

• Utilized in situ and ex vivo perfused organs with continuous weighing to measure transport.
• Employed transcytosis inhibitors (NEM, filipin) and tissue cooling to differentiate transport pathways.
• Examined transport in caveolin-1-deficient mice lacking plasmalemmal vesicles.

Main Results:

• High doses of NEM and filipin increased bulk macromolecule transport in isolated organs, despite vasoconstriction.
• In situ studies showed reduced albumin tracer uptake with NEM and filipin.
• Albumin transport exhibited low cooling sensitivity, indicating passive passage, and depended on capillary pressure and convection.
• LDL transport showed a cooling-sensitive, non-selective component.

Conclusions:

• Evidence largely supports passive transendothelial passage for most plasma macromolecules, particularly albumin.
• Active transcytosis may not be the primary mechanism for bulk transport of major plasma proteins.
• Specific, regulated transport of certain substances, akin to the blood-brain barrier, remains a possibility in peripheral capillaries.