Permeability enhancing effect of oleic acid and its mechanism in human alveolar A549 cells

We studied the mechanism of permeability enhancement by oleic acid (OA) using alveolar type-II-like human lung adenocarcinoma A549 cell monolayers. OA induced a transient rise of intracellular Ca2+ level over a few minutes and subsequently enhanced paracellular permeability to FITC-dextran. This Ca2+ rise was suppressed almost completely by calmodulin antagonists, calmodulin-dependent protein kinase inhibitors or removal of extracellular Ca2+ and partially by Ca2+-channel blockers and a protein kinase C inhibitor. The inhibition of OA-induced absorption enhancement was correlated with the suppression of Ca2+ influx increase. The inhibitors against protein kinase A, MLC kinase, phospholipase C, DAG lipase and DAG kinase did not affect the OA-induced absorption enhancement. These results suggested a possible permeability enhancing mechanism whereby OA activates calmodulin and calmodulin-dependent protein kinase-mediated Ca2+ channels, increases Ca2+ influx, and consequently enhances the junctional permeability.