title: Immature monocytes contribute to cardiopulmonary bypass-induced acute lung injury by generating inflammatory descendants.
abstract: As immune regulatory and effector cells, monocytes play an important role in the blood-extracorporeal circuit contact-related acute lung injury in patients undergoing cardiopulmonary bypass (CPB). However, circulating monocytes are phenotypically and functionally heterogeneous, so we characterised how immature monocytes affect acute lung injury induced by CPB.
  
  
  
  The identification and dynamic changes in monocyte subsets were monitored by flow cytometry in patients undergoing CPB and in a rat model of CPB. The differentiation and migration of monocyte subsets were explored by in vitro cultures and adoptive transfer in the CPB rat model.
  
  
  
  We observed a dramatic increase of two monocyte subsets in the peripheral blood of patients undergoing CPB, involving tumour necrosis factor (TNF)-α-producing, mature intermediate CD14highCD16+monocytes and a novel immature CD14lowCD16-subset. The immature CD14lowCD16-monocytes possessed limited ability for TNF-α production, and failed to suppress T-cell proliferation mediated by T-cell receptor signalling. However, these immature cells were highly proliferative and could differentiate into TNF-α producing, mature CD14highCD16+monocytes. In the rat model of CPB, we further demonstrated that CPB induced migration of immature monocytes into the lungs, either from the bone marrow or from the spleen. Moreover, we confirmed the hypothesis that immature subsets could contribute to CPB-induced acute lung injury by giving rise to TNF-α producing descendants.
  
  
  
  The immature CD14lowCD16-monocytes might contribute to blood-circuit contact-induced acute lung injury by generating TNF-α-producing, mature monocytes. New strategies based on monocyte manipulation could be a promising therapeutic approach for minimising CPB-related lung injury.
authors.affiliation: Department of Cardiopulmonary Bypass, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.|Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Zhichen
authors.initials: Z
authors.lastname: Xing
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Cardiopulmonary Bypass, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.|Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Hao
authors.affiliation: Department of Cardiopulmonary Bypass, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.|Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiopulmonary Bypass, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.|Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Chunjing
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Department of Cardiopulmonary Bypass, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.|Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.|Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Gastroenterology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.|Shanghai Institute of Digestive Disease, Shanghai, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Dong
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Guoli
authors.initials: G
authors.lastname: Li
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cardiopulmonary Bypass, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.|Center for Cardiac Intensive Care, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiaotong
authors.initials: X
authors.lastname: Hou
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000276:immunology*; D019264:Adoptive Transfer; D000328:Adult; D000368:Aged; D000818:Animals; D002315:Cardiopulmonary Bypass; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D010641:Phenotype; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: ARDS; Innate Immunity; Macrophage Biology