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Atherosclerosis. 1988 Jul;72(1):19-27.

Generation of reactive oxygen metabolites by phagocytosing endothelial cells.

Author information

1
Thrombosis Research Unit, King's College School of Medicine and Dentistry, London, U.K.

Abstract

We have studied the ability of particulate stimuli to induce the release of reactive oxygen metabolites from sub-cultured monolayers of human endothelial cells. Basal release of superoxide (O2-) and hydrogen peroxide from undisturbed monolayers was very low (108 pmol O2- and 75 pmol H2O2 in 3 h from dishes of 3 X 10(5) cells). Addition of 1-micron diameter polystyrene microspheres, which were phagocytosed by the cells progressively, caused a dramatic increase in release of both metabolites; by 3 h, a 13.5- and 6.6-fold increase over controls was observed respectively (P less than 0.001). Addition of formaldehyde-fixed human platelets or chylomicron-size lipid particles also increased production of reactive oxygen species. Similar rises in H2O2 and O2- production were induced by treatment with 10(-7) M phorbol myristate acetate. Pretreatment of endothelial cells with neuraminidase, heparinase or heparitinase to alter their glycocalyx composition substantially enhanced the effect of microspheres on H2O2 and O2- generation. We conclude that the interactions of particles, including platelets and lipids, with endothelial cells leads to the generation of significant pericellular levels of reactive oxygen species. These metabolites can oxidise a wide variety of nearby molecules, leading to cell damage and altered uptake characteristics for lipoproteins containing peroxidized lipids. These effects are exacerbated when endothelial cell glycocalyx composition is disrupted.

PMID:
2850806
DOI:
10.1016/0021-9150(88)90058-5
[Indexed for MEDLINE]

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