Contribution of monocyte and macrophage extracellular traps to neutrophilic airway inflammation in severe asthma

  • Quoc Quang Luu
    Department of Allergy and Clinical Immunology, Ajou University School of Medicine Department of Biomedical Sciences, Ajou University School of Medicine
  • Cao Thi Bich Tra
    Department of Allergy and Clinical Immunology, Ajou University School of Medicine Department of Biomedical Sciences, Ajou University School of Medicine
  • Moon Ji-Young
    Department of Allergy and Clinical Immunology, Ajou University School of Medicine
  • Jang Jae-Hyuk
    Department of Allergy and Clinical Immunology, Ajou University School of Medicine
  • Shin Yoo Seob
    Department of Allergy and Clinical Immunology, Ajou University School of Medicine
  • Choi Youngwoo
    Department of Allergy and Clinical Immunology, Ajou University School of Medicine
  • Ryu Min Sook
    Department of Allergy and Clinical Immunology, Ajou University School of Medicine
  • Park Hae-Sim
    Department of Allergy and Clinical Immunology, Ajou University School of Medicine Department of Biomedical Sciences, Ajou University School of Medicine

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<p>Background: Increased blood/sputum neutrophil counts are related to poor clinical outcomes of severe asthma (SA), where we hypothesized that classical monocytes (CMs)/CM-derived macrophages (Mφ) are involved. We aimed to elucidate the mechanisms of how CMs/Mφ induce the activation of neutrophils/innate lymphoid cells (ILCs) in SA.</p><p>Methods: Serum levels of monocyte chemoattractant protein-1 (MCP-1) and soluble suppression of tumorigenicity 2 (sST2) were measured from 39 patients with SA and 98 those with nonsevere asthma (NSA). CMs/Mφ were isolated from patients with SA (n = 19) and those with NSA (n = 18) and treated with LPS/interferon-gamma. Monocyte/M1Mφ extracellular traps (MoETs/M1ETs) were evaluated by western blotting, immunofluorescence, and PicoGreen assay. The effects of MoETs/M1ETs on neutrophils, airway epithelial cells (AECs), ILC1, and ILC3 were assessed in vitro and in vivo.</p><p>Results: The SA group had significantly higher CM counts with increased migration as well as higher levels of serum MCP-1/sST2 than the NSA group. Moreover, the SA group had significantly greater production of MoETs/M1ETs (from CMs/M1Mφ) than the NSA group. The levels of MoETs/M1ETs were positively correlated with blood neutrophils and serum levels of MCP-1/sST2, but negatively correlated with FEV1%. In vitro/in vivo studies demonstrated that MoETs/M1ETs could activate AECs, neutrophils, ILC1, and ILC3 by increased migration as well as proinflammatory cytokine production.</p><p>Conclusions: CM/Mφ-derived MoETs/M1ETs could contribute to asthma severity by enhancing neutrophilic airway inflammation in SA, where modulating CMs/Mφ may be a potential therapeutic option.</p>

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