Modulation of endothelial permeability by 1-O-alkylglycerols

ABSTRACT Regulation of endothelial barrier function often occurs through signalling involving phospholipase C activation which produces diacylglycerol (DAG), a lipidic second messenger activator of protein kinase C (PKC). Therefore, modification of lipidic composition of endothelial cell membranes might modify DAG production and, as a result, alter regulation of endothelial permeability. We investigated the in vitro effects of natural 1‐O‐alkylglycerols on porcine aortic endothelial cell permeability to dye‐labelled albumin. [3H]‐1‐O‐alkylglycerols (10 μm) were substantially incorporated into phosphatidylcholine (6.6%) and phosphatidylethanolamine (4.4%). Stimulation of endothelial cell monolayer with phorbol‐myristate‐acetate or with the calcium ionophore A23187 resulted in a raise in permeability to albumin. Pre‐treatment with 1‐O‐alkylglycerols (10 μm, 24 h) had no effect on basal albumin permeability but totally inhibited the effect of phorbol‐myristate‐acetate, and brought the permeability of A23187‐stimulated endothelial cell monolayers below control. After incubation of cells with [3H]‐1‐O‐alkylglycerols (10 μm, 24 h), we detected the production of the analogue of DAG, and PKC inhibitor, [3H]‐1‐O‐alkyl‐2‐acyl‐glycerol, in resting cells. This production was increased by 58% under A23187 stimulation while phorbol‐myristate‐acetate had no effect. Our data demonstrate that natural 1‐O‐alkylglycerols modify endothelial permeability, and suggest that this effect could be mediated through alteration of lipidic signalling.