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

Yong Ho Kim,Edward D Crandall,David Z D'Argenio,Kwang-Jin Kim

doi:10.3390/membranes11050331

Abstract

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 (Papp) in the absence/presence of calcium chelator EGTA to determine the effects of perturbing tight junctions on “equivalent” pores. Papp across RAECM-I and -II in the absence of EGTA are similar and decrease as solute size increases. We modeled Papp 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.

Highlights

Ion permeability and strand numbers of tight junctions appear to be widely different in various epithelial models studied under different experiment conditions [7,8,9,10,11], equivalent aqueous pores appear to be in the range of
The numbers for small and large equivalent pores are 9.15 × 1011 and 1.88 × 105, respectively (Table 4), which account for 99.97% and 0.03% of respective total equivalent pore area (Table 5). These results suggest that passive restricted diffusion of hydrophilic solutes across rat alveolar epithelial cell monolayers (RAECM)-I
Small and large equivalent pore characteristics of RAECM-I monolayers were reported previously [39,40], their results were weakened by use of an inadequate number of hydrophilic solutes of 0.2–0.8 nm radius

Summary

Introduction

Passive transport properties of alveolar epithelium are thought to be governed primarily by the tight junctions between adjacent pneumocytes [3,4]. Characterization of tight junctions is essential for understanding the barrier properties of alveolar epithelium [3,5]. It is generally accepted that tight junctions contain aqueous pores whose properties (e.g., size, number, permeability, and selectivity) govern passive transport of hydrophilic solutes (including water and small inorganic ions) across epithelial barriers [6]. Ion permeability and strand numbers of tight junctions appear to be widely different in various epithelial models studied under different experiment conditions [7,8,9,10,11], equivalent aqueous pores appear to be in the range of

Methods

Results

Conclusion