title: Cigarette smoke attenuates phagocytic ability of macrophages through down-regulating Milk fat globule-EGF factor 8 (MFG-E8) expressions.
abstract: Chronic obstructive pulmonary disease (COPD) is one of the most common inflammatory diseases resulting from habitual smoking. Impaired clearance of apoptotic cell by airway macrophages contributes to lung inflammation. Milk fat globule-EGF factor 8 (MFG-E8), as a link between apoptotic cells and phagocytes, facilitates clearance of apoptotic cells and attenuates inflammation. We sought to investigate altered expression and potential role of MFG-E8 in COPD. In this study, apoptosis was increased and the level of MFG-E8 was decreased while HMGB1 expression was increased in lung tissues of CS-exposed mice. Compared with CS-exposed WT mice, more apoptotic cells were accumulated in lung tissues of CS-exposed MFG-E8 deficiency mice. Exposure of a range of macrophages to cigarette smoke extract (CSE) resulted in decreased MFG-E8 expression. Administration of rmMFG-E8 ameliorated phagocytic ability of RAW264.7 cells and suppressed inflammatory response induced by CS-exposure. 10% CSE stimulation suppressed Rac1 membrane localization in RAW264.7 cells which was restored by administration of rmMFG-E8. MFG-E8 deficiency diminished uptake of apoptotic thymocytes by peritoneal macrophages upon CSE exposure. Overall, the findings in current work provide a novel target for diagnosing and treating COPD.
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Yueqin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Guangwei
authors.initials: G
authors.lastname: Luo
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Hu
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Guilian
authors.initials: G
authors.lastname: Cheng
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Jia
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Bingtao
authors.initials: B
authors.lastname: Su
authors.affiliation: Department of Respiratory Medicine, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Nian
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Laboratory of Clinical Immunology, Wuhan No. 1 Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China.
authors.forename: Tianpen
authors.initials: T
authors.lastname: Cui
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics; D016207:Cytokines / Q000378:metabolism; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008894:Milk Proteins / Q000235:genetics*; D010587:Phagocytosis / Q000276:immunology*; D000067996:RAW 264.7 Cells; D012907:Smoking / Q000009:adverse effects*; D060168:Thymocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000954:Antigens, Surface; D016207:Cytokines; D024243:HMGB1 Protein; D018836:Inflammation Mediators; C490919:Mfge8 protein, mouse; D008894:Milk Proteins