{
  "abstract": "Neutrophil recruitment to the lungs is elevated in COPD patients. Lung endothelial cells are fundamental in neutrophil recruitment, attachment and diapedesis. Red blood cell-derived iron (heme) is increased in COPD alveoli; heme can cause endothelial dysfunction, specifically increased inflammatory responses and junctional permeability. Neutrophilic inflammation in COPD is associated with bacterial colonisation including H. influenzae and M. catarrhalis. We evaluated the influence of H. influenzae and M. catarrhalis on endothelial cell- neutrophil adhesion, and assessed if heme altered the effects of bacterial exposure on endothelial cells.Lung endothelial cells (HULEC-5a) were exposed to either H. influenzae or M. catarrhalis, at MOI 5:1 for 24h following pe-treated with/without heme (50 µM or 100 µM) for 24h. Neutrophil-endothelial adhesion was assessed using fluorescently labelled neutrophils, quantitative measurement of fluorescence by microplate reader and confirmed observationally by microscopy (n=12). Endothelial cell expression of neutrophil adhesion genes (ICAM-1, VCAM-1 and E-Selectin) was measured using RT-qPCR (n=8).Endothelial cells exposed to H. influenzae and M. catarrhalis significantly upregulated expression of adhesion genes. M. catarrhalis induced upregulation of ICAM-1, E-Selectin and VCAM-1 (91.1, 130.3 and 3.6 fold respectively, p<0.05 for all). H. influenzae increased ICAM-1 and E-Selectin (91.1 and 139.8 fold respectively, p<0.01 for all). M. catarrhalis, but not H. influenzae, significantly elevated neutrophil adhesion (p<0.0001). Pre-treatment with heme had no significant effect on bacteria induced adhesion gene expression or neutrophil adhesion.Endothelial cell expression of genes involved in neutrophil recruitment and adhesion are modulated by exposure to pathogenic bacteria H. influenzae and M. catarrhalis, with the latter also functionally increasing neutrophil adhesion. Heme did not directly affect neutrophil adhesion to the endothelium. Bacterial modulation of neutrophil migration through the endothelium may be a feature of endothelial dysfunction, amplifying neutrophilic inflammation and increasing exacerbation risk in COPD patients.",
  "authors": [
    {
      "affiliations": [
        "University of Manchester, Manchester, UK",
        "Medicines Evaluation Unit, Manchester, UK"
      ],
      "name": "M Wilcox"
    },
    {
      "affiliations": [
        "University of Manchester, Manchester, UK"
      ],
      "name": "J Baker"
    },
    {
      "affiliations": [
        "University of Manchester, Manchester, UK"
      ],
      "name": "H Deka"
    },
    {
      "affiliations": [
        "University of Manchester, Manchester, UK",
        "Medicines Evaluation Unit, Manchester, UK"
      ],
      "name": "D Singh"
    },
    {
      "affiliations": [
        "University of Manchester, Manchester, UK"
      ],
      "name": "S Lea"
    }
  ],
  "title": "S59 Effects of bacteria and heme on neutrophil-endothelial interactions in COPD",
  "uid": "c605bcc3-8aee-53ec-9014-86eb55402294"
}