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Zinc and zinc transporters in human alveolar and THP-1 macrophages and roles in phagocytosis/efferocytosis

Peter Zalewski, Rhys Hamon, Hai Tran, Hubertus Jersmann, Sandra Hodge, Mariea Bosco
European Respiratory Journal 2014 44: P1474; DOI:
Peter Zalewski
1Discipline of Medicine, University of Adelaide, Woodville, South Australia, Australia
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Rhys Hamon
1Discipline of Medicine, University of Adelaide, Woodville, South Australia, Australia
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Hai Tran
1Discipline of Medicine, University of Adelaide, Woodville, South Australia, Australia
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Hubertus Jersmann
2Department of Thoracic Medicine Lung Research Laboratory, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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Sandra Hodge
2Department of Thoracic Medicine Lung Research Laboratory, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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Mariea Bosco
1Discipline of Medicine, University of Adelaide, Woodville, South Australia, Australia
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Abstract

Impaired efferocytic clearance of apoptotic epithelial cells by alveolar macrophages (AM) occurs in chronic obstructive pulmonary disease (COPD) and leads to a pro-inflammatory state. Zinc (Zn) deficiency in mice exacerbates lung inflammation and results in an accumulation of apoptotic epithelial cells. Zn may be an important factor in monocyte/macrophage differentiation and efferocytosis. Concentrations of Zn were significantly reduced in the bronchoalveolar lavage (BAL) of patients with COPD who are current smokers. BAL Zn was positively correlated with AM efferocytic ability and there was decreased efferocytosis in in vitro Zn depleted AM. In human THP-1 cells, monocyte differentiation to macrophages was accompanied by an 8-fold increase in cytosolic Zn, 41-fold and 26-fold increases in mRNA levels for two SLC30A Zn transporters ZnT3 and ZnT4, respectively, and smaller increases in several SLC39A Zn transporters (including ZIP1, ZIP13 and ZIP14). In Zn depleted macrophages, the only increase (32-fold) was in the SLC39A Zn transporter ZIP2. ZIP1 and ZIP14 were localized to the plasma membrane while ZIP2 was localized to the cytoplasm, perinuclear region and nucleoli. ZnT3 and ZnT4 were predominantly in intracellular vesicles although ZnT4 was also found in the trans-Golgi, where it is likely involved in incorporation of Zn into metalloproteins. Finally, macrophages of mice with knockout of ZIP1 had significantly reduced intracellular Zn and efferocytosis capability. We propose that Zn homeostasis in macrophages involves the coordinated action of several Zn transporters and that these play important roles in macrophage differentiation, efferocytosis and cell survival.

  • Monocyte / Macrophage
  • Anti-inflammatory
  • COPD - mechanism
  • © 2014 ERS
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Zinc and zinc transporters in human alveolar and THP-1 macrophages and roles in phagocytosis/efferocytosis
Peter Zalewski, Rhys Hamon, Hai Tran, Hubertus Jersmann, Sandra Hodge, Mariea Bosco
European Respiratory Journal Sep 2014, 44 (Suppl 58) P1474;

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Zinc and zinc transporters in human alveolar and THP-1 macrophages and roles in phagocytosis/efferocytosis
Peter Zalewski, Rhys Hamon, Hai Tran, Hubertus Jersmann, Sandra Hodge, Mariea Bosco
European Respiratory Journal Sep 2014, 44 (Suppl 58) P1474;
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