• Surgical infections · Jan 2002

    Endothelium down-regulates Fas, TNF, and TRAIL-induced neutrophil apoptosis.

    • Steven D Tennenberg, Raphaela Finkenauer, and Tao Wang.
    • Department of Surgery, John D. Dingell Veterans Affairs Medical Center, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. steven.tennenberg@med.va.gov
    • Surg Infect (Larchmt). 2002 Jan 1; 3 (4): 351-7.

    BackgroundNeutrophil (PMN) apoptosis regulates PMN functional longevity and is integral to the resolution of inflammation. We have recently shown that PMN contact with an endothelial monolayer down-regulates spontaneous PMN apoptosis. We sought to explore endothelial-mediated down-regulation of PMN apoptosis following mediator-induced apoptosis. We tested the three known membrane-initiated, receptor-ligand apoptotic pathways: Fas, tumor necrosis factor-alpha (TNF), and TNF-related apoptosis inducing ligand (TRAIL).MethodsPMNs were isolated from peripheral venous blood of healthy volunteers. PMNs were co-cultured in the absence and presence of a human coronary artery endothelial cell (HCAEC) monolayer for 4 h. PMNs were then stimulated with the pro-apoptotic agonists (agonistic anti-Fas IgM, TNF, and TRAIL) for one hour, followed by an assessment of apoptosis after 5 h. PMN apoptosis was measured using an acridine orange/ethidium bromide in situ fluorescent microscopy assay. Caspase 3 activity was assessed using a spectrophotometric assay.ResultsIn addition to spontaneous PMN apoptosis, endothelial co-culture resulted in significant increases in the percentages of normal cells and decreased percentages of apoptotic cells after stimulation with agonistic anti-Fas IgM, TNF and TRAIL. Endothelial co-culture did not alter PMN caspase 3 activity.ConclusionEndothelial-mediated down-regulation of PMN apoptosis is conferred after 4 h of co-culture. In addition to spontaneous apoptosis, endothelial contact down-regulated the three known membrane-initiated PMN apoptotic pathways: Fas, TNF, and TRAIL. These data imply that endothelial-mediated down-regulation of PMN apoptosis may involve defects in each apoptotic pathway or a single defect in a distal transduction or effector event common to all three pathways. Alterations in the activity of caspase 3 did not appear to serve as a mechanism for endothelial-mediated down-regulation of PMN apoptosis.

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