title: Temporal and spatial characterization of mononuclear phagocytes in circulating, lung alveolar and interstitial compartments in a mouse model of bleomycin-induced pulmonary injury.
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 Ly6C(hi) 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 Ly6C(hi)-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.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, 220, Cheng-Lin Road, Tianjin 300162, China; Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, 220, Cheng-Lin Road, Tianjin 300162, China. Electronic address: wenjieji@gmail.com.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Ji
authors.affiliation: Department of Respiratory and Critical Care Medicine, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, 220, Cheng-Lin Road, Tianjin 300162, China; Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, 220, Cheng-Lin Road, Tianjin 300162, China.
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Ma
authors.affiliation: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, 220, Cheng-Lin Road, Tianjin 300162, China; Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, 220, Cheng-Lin Road, Tianjin 300162, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Respiratory and Critical Care Medicine, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, 220, Cheng-Lin Road, Tianjin 300162, China; Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, 220, Cheng-Lin Road, Tianjin 300162, China.
authors.forename: Yi-Dan
authors.initials: YD
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, 220, Cheng-Lin Road, Tianjin 300162, China; Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, 220, Cheng-Lin Road, Tianjin 300162, China.
authors.forename: Rui-Yi
authors.initials: RY
authors.lastname: Lu
authors.affiliation: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, 220, Cheng-Lin Road, Tianjin 300162, China; Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, 220, Cheng-Lin Road, Tianjin 300162, China.
authors.forename: Hai-Ying
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, 220, Cheng-Lin Road, Tianjin 300162, China; Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, 220, Cheng-Lin Road, Tianjin 300162, China.
authors.forename: Zhao-Zeng
authors.initials: ZZ
authors.lastname: Guo
authors.affiliation: Department of Radiology, Northwestern University, 737 N. Michigan Ave, Chicago, IL 60611, USA.
authors.forename: Zhuoli
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, 220, Cheng-Lin Road, Tianjin 300162, China; Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, 220, Cheng-Lin Road, Tianjin 300162, China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Li
authors.affiliation: Department of Respiratory and Critical Care Medicine, Pingjin Hospital, Logistics University of the Chinese People's Armed Police Forces, 220, Cheng-Lin Road, Tianjin 300162, China. Electronic address: luqing-wei@163.com.
authors.forename: Lu-Qing
authors.initials: LQ
authors.lastname: Wei
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D000950:Antigens, Ly / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D039521:CD11c Antigen / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D018836:Inflammation Mediators / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000145:classification / Q000276:immunology* / Q000473:pathology; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism; D013997:Time Factors
chemical_list: D000943:Antigens, Differentiation; D000950:Antigens, Ly; D015415:Biomarkers; D039521:CD11c Antigen; D018836:Inflammation Mediators; D037181:Lectins, C-Type; C494192:Ly-6C antigen, mouse; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; C036763:monocyte-macrophage differentiation antigen; D001761:Bleomycin
keywords: Bleomycin; Lung macrophage; Macrophage polarization; Monocyte subsets; Pulmonary fibrosis