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Dynamic changes of mononuclear phagocytes in circulating, pulmonary alveolar and interstitial compartments in a mouse
Guo-An Xiang1, Yi-Dan Zhang1, Cheng-Cheng Su1
1a Department of Respiratory and Critical Care Medicine , Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces , Tianjin , China , and.
Context:
Silicosis is a devastating, irreversible lung fibrosis condition exposed to crystalline silica. The mononuclear phagocyte system plays an important role in the pathogenesis of silicosis.
Objective:
The present study was aimed to explore the dynamic changes of mononuclear phagocytes in circulating, pulmonary alveolar and interstitial compartments in experimental silicosis model.
Materials And Methods:
A mouse model of lung fibrosis was developed with crystalline silica particles (2 mg/40 μL via oropharyngeal instillation) using male C57BL/6 mice, and were killed on days 1, 3, 7, 14, and 28. The lung inflammation and fibrosis was investigated using hematoxylin-eosin staining and bronchoalveolar lavage fluid (BALF) analysis, Masson's trichrome staining, and immunofluorescence. Circulating monocyte subsets (Ly6C(hi) and Ly6C(lo)), polarization state of BALF-derived alveolar macrophages (AMϕ) and lung interstitial macrophages (IMϕ, derived from enzymatically digested lung tissue) were analyzed by flow cytometry.
Results:
The percentage of Ly6C(hi) monocytes significantly increased on day 1 after silica exposure, which reached the peak level from day 7 till day 28. Moreover, M2 (alternative activation) AMϕ (PI - CD64 + CD206+) was dramatically and progressively increased from day 1 to day 28. A parallel increase in IMϕ with M2 polarization (PI-CD64 + CD11b + CD206+) was also observed from day 1 to day 28.
Conclusion:
Our data demonstrate a dynamic view of mononuclear phagocyte change in three compartments after silica challenge, which highlights the remodeling of mononuclear phagocyte system as a potential therapeutic target for silicosis.
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