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Effect of LysM+ macrophage depletion on lung pathology in mice with chronic bronchitis.

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  • معلومة اضافية
    • المصدر:
      Publisher: published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society Country of Publication: United States NLM ID: 101607800 Publication Model: Print Cited Medium: Internet ISSN: 2051-817X (Electronic) Linking ISSN: 2051817X NLM ISO Abbreviation: Physiol Rep Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: [Malden MA] : published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society, 2013-
    • الموضوع:
      Bronchitis, Chronic/*pathology ; Lung/*pathology ; Macrophages/*pathology; Animals ; Disease Models, Animal ; Mice ; Mice, Transgenic
    • نبذة مختصرة :
      Macrophages (MΦ) are key sentinels of respiratory exposure to inhaled environmental stimuli. In normal "healthy" tissues, MΦ are believed to be a dormant cell type that, upon exposure to stress-causing stimuli, may get activated to exhibit pro- or anti-inflammatory roles. To test whether stress present in chronic bronchitic (CB) airways triggers MΦ to manifest protective or detrimental responses, the DTA+ (LysM-regulated Diphtheria Toxin A expressing) strain with partial MΦ-deficiency was crossed with the Scnn1b-Tg mouse model of CB and the progenies were studied at 4-5 weeks of age. Compared with DTA- littermates, the DTA+ mice had ~50% reduction in bronchoalveolar lavage (BAL) MΦ, and the recovered MΦ were immature, phenotypically distinct, and functionally defective. DTA+/Scnn1b-Tg mice exhibited a similar depletion of LysM+ MΦ offset by a significant increase in LysM- MΦ in the BAL. In DTA+/Scnn1b-Tg mice, lung disease was more severe than in DTA-/Scnn1b-Tg littermates, as indicated by an increased incidence of mucus plugging, mucous cells, airway inflammation, higher levels of cytokines/chemokines (KC, TNF-α, MIP-2, M-CSF, IL-5, and IL-17), and worsened alveolar airspace enlargement. DTA+/Scnn1b-Tg mice exhibited increased occurrence of lymphoid nodules, which was concomitant with elevated levels of immunoglobulins in BAL. Collectively, these data indicate that numerical deficiency of MΦ in stressed airspaces is responded via compensatory increase in the recruitment of immature MΦ and altered non-MΦ effector cell-centered responses, for example, mucus production and adaptive immune defense. Overall, these data identify dynamic roles of MΦ in moderating, rather than exacerbating, the severity of lung disease in a model of CB.
      (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)
    • References:
      Allergy. 2015 Jan;70(1):80-9. (PMID: 25331546)
      J Immunol. 2009 Apr 1;182(7):4357-67. (PMID: 19299736)
      Front Immunol. 2017 Nov 24;8:1618. (PMID: 29225599)
      J Heart Lung Transplant. 2005 Jan;24(1):38-45. (PMID: 15653377)
      J Leukoc Biol. 2004 Apr;75(4):612-23. (PMID: 14726498)
      Transgenic Res. 1999 Aug;8(4):265-77. (PMID: 10621974)
      Am J Respir Cell Mol Biol. 2015 Jun;52(6):772-84. (PMID: 25360868)
      BMC Genomics. 2014 Sep 10;15:726. (PMID: 25204199)
      Physiol Rep. 2018 Apr;6(8):e13677. (PMID: 29667749)
      Genesis. 2007 Sep;45(9):593-605. (PMID: 17868096)
      Am J Respir Crit Care Med. 2008 Apr 1;177(7):730-42. (PMID: 18079494)
      Br J Pharmacol. 2009 Oct;158(4):1048-58. (PMID: 19845686)
      Am J Respir Cell Mol Biol. 2016 Feb;54(2):210-21. (PMID: 26121027)
      J Immunol. 2014 Oct 15;193(8):4245-53. (PMID: 25225663)
      J Exp Med. 2013 Sep 23;210(10):1977-92. (PMID: 24043763)
      Annu Rev Physiol. 1990;52:177-95. (PMID: 2184756)
      Nat Med. 2004 Sep;10(9):927-34. (PMID: 15311275)
      Science. 1997 Sep 26;277(5334):2002-4. (PMID: 9302297)
      Nat Med. 2004 May;10(5):487-93. (PMID: 15077107)
      Thorax. 2015 Dec;70(12):1189-96. (PMID: 26286722)
      Nature. 2014 Jan 16;505(7483):412-6. (PMID: 24317696)
      Mucosal Immunol. 2012 Jul;5(4):397-408. (PMID: 22419116)
    • Grant Information:
      P01 HL108808 United States HL NHLBI NIH HHS; P30 DK065988 United States DK NIDDK NIH HHS
    • Contributed Indexing:
      Keywords: Airway inflammation; MΦ depletion; Scnn1b transgenic mice; airway mucus obstruction; alveolar macrophages
    • الموضوع:
      Date Created: 20180419 Date Completed: 20190513 Latest Revision: 20240314
    • الموضوع:
      20250114
    • الرقم المعرف:
      PMC5904692
    • الرقم المعرف:
      10.14814/phy2.13677
    • الرقم المعرف:
      29667749