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Vitamin E attenuates the injurious effects of bioactive phospholipids on human ciliated epithelium in vitro

¹ Division of Pulmonology, Dept of Medicine, Johannesburg Hospital and University of the Witwatersrand, Johannesburg, South Africa, ² MRC Unit for Inflammation and Immunity, Dept of Immunology, University of Pretoria, South Africa, ³ Host Defence Unit, Dept of Thoracic Medicine, Imperial College of Science, Technology and Medicine, National Heart and Lung Institute, London, UK

CORRESPONDENCE: C. Feldman, Dept of Medicine, University of the Witwatersrand, Medical School, 7 York Road, Parktown 2193, Johannesburg, South Africa. Fax: 27 114884675

Keywords: airway inflammation, ciliary beat frequency, epithelial damage, lysophosphatidylcholine, platelet-activating factor, polymorphonuclear leukocytes

Received: May 15, 2000
Accepted March 10, 2001

Bioactive phospholipids (PL), particularly lysophosphatidylcholine (LPC), are being increasingly implicated in the pathogenesis of various acute and chronic inflammatory disorders, particularly those of the airways, while there is emerging evidence that vitamin E may function as a natural antagonist of these lipid mediators of inflammation. The aims of this study were to document the effects of vitamin E on the inhibition of ciliary beating and damage to structural integrity of human ciliated epithelium induced by the PL, platelet-activating factor (PAF), lyso-PAF and LPC in vitro in relation to the anti-oxidative and membrane-stabilizing properties of the vitamin.

Ciliary beat frequency was measured by a phototransistor technique, and damage to structural integrity assessed by a visual-scoring index, while superoxide production by polymorphonuclear leukocytes and membrane-stabilizing potential were measured using lucigenin-enhanced chemiluminescence and haemolytic procedures, respectively.

All three PL caused inhibition of ciliary beating and structural damage to human ciliated epithelium by membrane-directed cytotoxic mechanisms, which were potentiated by human polymorphonuclear leukocytes due to induction of oxidant-mediated injury. Both direct and phagocyte-inflicted epithelial injury was attenuated by vitamin E. In haemolytic and chemiluminescence assays, vitamin E neutralized both the membrane-destabilizing and pro-oxidative actions of all three PL, while spectrophotometric analysis of mixtures of vitamin E with PAF, lyso-PAF and LPC revealed alterations in peak intensity, as well as peak shifts, indicative of physicochemical interactions between the vitamin and the PL.

Vitamin E status may be a determinant of susceptibility to phospholipid-mediated airway inflammation and damage.

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