Temporal and spatial characterization of mononuclear phagocytes in circulating, lung alveolar and interstitial compartments in a mouse model of bleomycin-induced pulmonary injury

Wen Jie Ji*, Yong Qiang Ma, Xin Zhou, Yi Dan Zhang, Rui Yi Lu, Hai Ying Sun, Zhao Zeng Guo, Zhuoli Zhang, Yu Ming Li, Lu Qing Wei

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The mononuclear phagocyte system, including circulating monocytes and tissue resident macrophages, plays an important role in acute lung injury and fibrosis. The detailed dynamic changes of mononuclear phagocytes in the circulating, lung alveolar and interstitial compartments in bleomycin-induced pulmonary injury model have not been fully characterized. The present study was designed to address this issue and analyzed their relationships with pulmonary pathological evolution after bleomycin challenge. A total of 100 male C57BL/6 mice were randomly divided to receive bleomycin (2.5mg/kg, n=50) or normal saline (n=50) via oropharyngeal approach, and were sacrificed on days 1, 3, 7, 14 and 21. Circulating monocyte subsets, polarization state of bronchoalveolar lavage fluid (BALF)-derived alveolar macrophages (AMφ) and lung interstitial macrophages (IMφ, derived from enzymatically digested lung tissue) were analyzed by flow cytometry. There was a rapid expansion of circulating Ly6Chi monocytes which peaked on day 3, and its magnitude was positively associated with pulmonary inflammatory response. Moreover, an expansion of M2-like AMφ (F4/80+CD11c+CD206+) peaked on day 14, and was positively correlated with the magnitude of lung fibrosis. The polarization state of IMφ remained relatively stable in the early- and mid-stage after bleomycin challenge, expect for an increase of M2-like (F4/80+CD11c-CD206+) IMφ on day 21. These results support the notion that there is a Ly6Chi-monocyte-directed pulmonary AMφ alternative activation. Our result provides a dynamic view of mononuclear phagocyte change in three compartments after bleomycin challenge, which is relevant for designing new treatment strategies targeting mononuclear phagocytes in this model.

Original languageEnglish (US)
Pages (from-to)7-16
Number of pages10
JournalJournal of Immunological Methods
Volume403
Issue number1-2
DOIs
StatePublished - Jan 31 2014

Keywords

  • Bleomycin
  • Lung macrophage
  • Macrophage polarization
  • Monocyte subsets
  • Pulmonary fibrosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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