Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease

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外文摘要：Increased levels of surfactant protein D(SP-D)and lipid-laden foamy macrophages(FMs)are frequently found under oxidative stress conditions and/or in patients with chronic obstructive pulmonary disease(COPD)who are also chronically exposed to cigarette smoke(CS).However,the roles and molecular mechanisms of SP-D and FMs in COPD have not yet been determined.In this study,increased levels of SP-D were found in the bronchoalveolar lavage fluid(BALF)and sera of ozone-and CS-exposed mice.Furthermore,SP-D-knockout mice showed increased lipid-laden FMs and airway inflammation caused by ozone and CS exposure,similar to that exhibited by our study cohort of chronic smokers and COPD patients.We also showed that an exogenous recombinant fragment of human SP-D(rfhSP-D)prevented the formation of oxidized low-density lipoprotein(oxLDL)-induced FMs in vitro and reversed the airway inflammation and emphysematous changes caused by oxidative stress and CS exposure in vivo.SP-D upregulated bone marrow-derived macrophage(BMDM)expression of genes involved in countering the oxidative stress and lipid metabolism perturbations induced by CS and oxLDL.Our study demonstrates the crucial roles of SP-D in the lipid homeostasis of dysfunctional alveolar macrophages caused by ozone and CS exposure in experimental mouse emphysema,which may provide a novel opportunity for the clinical application of SP-D in patients with COPD.

外文关键词：

Alveolar macrophagesChronic obstructive pulmonary diseasesSurfactant protein DLipid metabolismOzoneCigarettes

作者：

Miao-Hsi Hsieh、Pei-Chi Chen、Han-Yin Hsu、Jui-Chang Liu、Yu-Sheng Ho、Yuh Jyh Lin、Chin-Wei Kuo、Wen-Shuo Kuo、Hui-Fang Kao、Shulhn-Der Wang、Zhi-Gang Liu、Lawrence Shih-Hsin Wu、Jiu-Yao Wang

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作者单位：

Center for Allergy,Immunology,and Microbiome(A.I.M.),China Medical University Hospital,Taichung,Taiwan,China

Graduate Institute of Basic Medical Sciences,College of Medicine,National Cheng Kung University,Tainan,Taiwan,China

Department of Nursing,National Tainan Junior College of Nursing,Tainan,Taiwan,China

Graduate Institute of Biochemistry and Molecular Biology,College of Medicine,National Cheng Kung University,Tainan,Taiwan,China

Department of Pediatrics,National Cheng Kung University Hospital,Tainan,Taiwan,China

Division of Pulmonary Medicine,Department of Internal Medicine,National Cheng Kung University Hospital,College of Medicine,National Cheng Kung University,Tainan,Taiwan,China

Institute of Clinical Medicine,College of Medicine,National Cheng Kung University,Tainan,Taiwan,China

School of Chemistry and Materials Science,Nanjing University of Information Science and Technology,Nanjing,China

School of Post-Baccalaureate Chinese Medicine,China Medical University,Taichung,Taiwan,China

Department of Respirology and Allergy,Third Affiliated Hospital of Shenzhen University,Shenzhen,China

Institute of Biomedical Sciences,China Medical University,Taichung,Taiwan,China

Department of Allergy,Immunology,and Rheumatology(AIR),China Medical University Children's Hospital,Taichung,Taiwan,China

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基金：

Ministry of Science and Technology(MOST)of TaiwanMinistry of Science and Technology(MOST)of TaiwanHeadquarters of University Advancement at the National Cheng Kung UniversityMinistry of Education in Taiwana research grant from the Center for Allergy,Immunology,and Microbiome(A.I.M.),China Medical University Hospital,Taichung,Taiwan

项目编号：

103-2321-B-006-030104-2321-B-006-0081JA8

出版年：

2023

DOI：

10.1038/s41423-022-00946-2

中国免疫学杂志(英文版)

中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI

影响因子：0.731

ISSN：1672-7681

年,卷(期)：2023.20(1)

参考文献量45