Untitled

Abstract

Pulmonary exposure to oleic acid (OA) is associated with permeability alterations and cellular damage; however, the exact relationship between these two effects has not been clearly established. Using cultured alveolar epithelial monolayers, we demonstrated that OA and some other fatty acids (< or = 50 microM) can induce permeability changes without detectable cellular damage. At higher concentrations, however, OA caused severe membrane damage and leakage to solute flux. The permeability enhancing effect of OA was observed with both the paracellular marker 3H-mannitol and the lipophilic transcellular indicator 14C-progesterone. While the effect of OA on transcellular permeability may be attributed to its known effect on membrane fluidity, the paracellular promoting effect of OA and its mechanism are not well established. We postulated that OA may increase paracellular permeability through a Ca(2+)-dependent tight junction mechanism. Using dual-excitation fluorescence microscopy, we demonstrated that OA can increase intracellular calcium, [Ca2+]i, in a dose-dependent manner. This effect was transient at low OA concentrations (< or = 50 microM) but became more pronounced and sustained at higher concentrations. Free hydroxyl and unsaturated groups were required for this activation since esterified OA (oleic methyl ester) and stearic acid (a saturated fatty acid with equal chain length) had much reduced effects on both the [Ca2+]i and the permeability alterations. Degree of unsaturation was unimportant since linolenic acid (18:3), linoleic acid (18:2), and OA (18:1) had similar and comparable effects on the two parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Putrescine Uptake by Alveolar Epithelial Cell Monolayers Exhibiting Differing Transepithelial Electrical Resistances

“…The mannitol permeabilities measured are similar to those previously reported for alveolar type I cells cultured on Transwells. 9,17 As expected the permeability of the low resistance monolayers to [ 14 C]mannitol was higher than for the monolayers exhibiting high resistances.…”

“…By using this method, several investigations have been reported which examine the pulmonary epithelial permeability of various compounds. [5][6][7][8][9][10][11] However both laboratories have published little data characterizing the monolayers further than TEER, generally assuming that the characterization carried out on cells grown in plastic culture wells can be extrapolated to those plated on inserts. This is despite well-documented evidence that the substrata on which alveolar type II cells are cultured can have profound effects on the state of de-differentiation.…”

Liver Targeting Liposomes Containing .BETA.-Sitosterol Glucoside with Regard to Penetration-Enhancing Effect on HepG2 Cells.

“…The FD-4 solution used in these experiments contained 1% DMSO to disperse these enhancers uniformly because of their fairly low solubility in water. Oleic acid was used as an active control as it is often used as a penetration enhancer by increasing the motional freedom or fluidity of membrane phospholipids, 21) and is capable of nonspecific disruption of the alveolar membrane at high concentrations (0.1 mM). 21,22) The association of FD-4 was not enhanced by 100 mM oleic acid at 37°C, showing the same value as at 4°C and control (FD-4 solution containing 1% DMSO), but Sit-G (100 mM) significantly increased it at 37°C as compared that with at 4°C.…”

Application of Sterylglucoside-Containing Particles for Drug Delivery

“…model of macromolecules that did not associate with HepG2 cells when incubated at 37˚C. Application of oleic acid increased drug absorption of dermal [85] and mucosal [86,87] drug delivery systems, although the association of FD-4 was not enhanced by oleic acid in such conditions. Incorporation of Sit-G increased the association of FD-4 in HepG2 cells.…”