Paracellular porosity and pore size of the human intestinal epithelium in tissue and cell culture models.
The paracellular space defines the passive permeation of hydrophilic compounds in epithelia. The goal of this study was to characterise the paracellular permeation pathway in the human intestinal wall and differentiated epithelial cell models (MDCKII, Caco-2 and 2/4/A1). The permeabilities of hydrophilic polyethylene glycols (PEG) were investigated in diffusion chambers, and mass spectrometry was used to obtain accurate concentrations for each PEG molecule. The paracellular porosity and the size of the pores in the membranes were estimated from the PEG permeability data using an effusion-based approach. The porosities were found to be low (fraction 10(-7)-10(-5) of the epithelial surface) in all investigated membranes. Two different pore sizes (radii 5-6 and >10 A) were detected in the human intestinal epithelium and the Caco-2 and MDCKII cells, while only one (about 15 A) in the 2/4/A1 monolayer. The paracellular porosities of the human small intestine and 2/4/A1 monolayers were larger (>10(-7)) than that of the MDCKII and Caco-2 cells (<10(-7)). We report for the first time the quantitative values describing both porosity and pore size of the paracellular space in the human intestine. The cell models deviate from the small intestine either with respect to porosity (Caco-2, MDCKII) or pore size distribution (2/4/A1).
Linnankoski
Johanna
J
Centre for Drug Research, University of Helsinki, Helsinki, Finland.
Mäkelä
Johanna
J
Palmgren
Joni
J
Mauriala
Timo
T
Vedin
Charlotta
C
Ungell
Anna-Lena
AL
Lazorova
Lucia
L
Artursson
Per
P
Urtti
Arto
A
Yliperttula
Marjo
M
D000818:Animals; D018938:Caco-2 Cells; D002460:Cell Line; D002463:Cell Membrane Permeability; D004285:Dogs; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics*
D011092:Polyethylene Glycols