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Capillary endothelial surface layer selectively reduces plasma solute distribution volume.

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Summary

The endothelial surface layer acts as a barrier, restricting large molecules like Dextran 70. Molecular size and charge significantly influence how tracers penetrate this barrier, affecting capillary permeability.

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Area of Science:

  • Vascular Biology
  • Capillary Permeability
  • Endothelial Surface Layer

Background:

  • The endothelial surface layer (ESL) is a crucial component of the capillary barrier.
  • Previous work showed ESL confines Dextran 70 (70 kDa) in hamster cremaster muscle capillaries.

Purpose of the Study:

  • To investigate the barrier properties of the ESL using various plasma tracers.
  • To determine the influence of molecular size and charge on tracer penetration into the ESL.

Main Methods:

  • Combined fluorescence and brightfield intravital microscopy.
  • Utilized a variety of plasma tracers including neutral and anionic dextrans, free dye (rhodamine), fibrinogen, and albumin.
  • Measured tracer equilibration and permeation rates into the ESL.

Main Results:

  • No permeation of ESL by neutral/anionic dextrans ≥70 kDa.
  • Rapid equilibration of neutral Dextran 40 (40 kDa) and rhodamine (0.4 kDa) with ESL.
  • Slow, size-dependent permeation of small anionic tracers (0.4–40 kDa) into ESL.
  • Fibrinogen (340 kDa) and albumin (67 kDa) penetrated ESL at similar rates (τ50 ≈ 40 min).
  • Dextran 70 conjugated to albumin entered ESL at the same rate as free albumin.

Conclusions:

  • ESL penetration is significantly affected by molecular size and charge for anionic molecules.
  • Multiple factors, including size, charge, and structure, influence protein penetration into the ESL.
  • The ESL acts as a size- and charge-selective barrier influencing capillary exchange.