4.5 Article

Characteristics of Passive Solute Transport across Primary Rat Alveolar Epithelial Cell Monolayers

Journal

MEMBRANES
Volume 11, Issue 5, Pages -

Publisher

MDPI
DOI: 10.3390/membranes11050331

Keywords

paracellular permeability; equivalent aqueous pores; tight junctions; barrier properties; air-blood barrier

Funding

  1. National Institutes of Health [P41EEB001978, R01ES017034, U01HL108364]
  2. Whittier Foundation
  3. Hastings Foundation
  4. Alfred E. Mann Institute at USC
  5. Will Rogers Motion Picture Pioneers Foundation

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The study found that passive diffusion of hydrophilic solutes across rat alveolar epithelial cells occurs through small and large equivalent pores, reflecting interactions of transmembrane proteins expressed in the intercellular tight junctions of the cells.
Primary rat alveolar epithelial cell monolayers (RAECM) were grown without (type I cell-like phenotype, RAECM-I) or with (type II cell-like phenotype, RAECM-II) keratinocyte growth factor to assess passive transport of 11 hydrophilic solutes. We estimated apparent permeability (P-app) in the absence/presence of calcium chelator EGTA to determine the effects of perturbing tight junctions on equivalent pores. P-app across RAECM-I and -II in the absence of EGTA are similar and decrease as solute size increases. We modeled P-app of the hydrophilic solutes across RAECM-I/-II as taking place via heterogeneous populations of equivalent pores comprised of small (0.41/0.32 nm radius) and large (9.88/11.56 nm radius) pores, respectively. Total equivalent pore area is dominated by small equivalent pores (99.92-99.97%). The number of small and large equivalent pores in RAECM-I was 8.55 and 1.29 times greater, respectively, than those in RAECM-II. With EGTA, the large pore radius in RAECM-I/-II increased by 1.58/4.34 times and the small equivalent pore radius increased by 1.84/1.90 times, respectively. These results indicate that passive diffusion of hydrophilic solutes across an alveolar epithelium occurs via small and large equivalent pores, reflecting interactions of transmembrane proteins expressed in intercellular tight junctions of alveolar epithelial cells.

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