Cross-talk between minimally primed HL-60 cells and resting HUVEC reveals a crucial role for adhesion over extracellularly released oxidants.
This study demonstrates that a long-lasting co-culture of neutrophil surrogates (HL-60 cells), minimally primed by platelet activating factor (PAF), and resting endothelial cells (EC) results in the elaboration of an hyper-adhesive endothelial surface, as measured by the increase in the expression of endothelial adhesion molecules E-Selectin, VCAM-1, and ICAM-1. This endothelial dysfunction is mediated by the activation of the redox-sensitive transcription factor NF-κB through an exclusive adhesion-driven mechanism active in the endothelial cell: reactive oxygen and nitrogen species, extracellularly released by minimally primed HL-60 cells, are not involved in the induction of the endothelial dysfunction. By exploring for the first time the potential for minimally primed neutrophil surrogates to induce endothelial dysfunction, this study suggests a novel mechanism which may be operative in pathologies, mediated by minimally primed neutrophils, such as hyperdyslipidemia and cardiovascular complications.
Dipartimento Farmacochimico, Tossicologico e Biologico, Università di Palermo, Italy.
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D002448:Cell Adhesion; D002460:Cell Line; D018920:Coculture Techniques; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D018922:HL-60 Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020239:Receptor Cross-Talk; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D019040:E-Selectin; D016328:NF-kappa B; D016877:Oxidants; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1