M1/M2型肺泡巨噬细胞亚群在新型冠状病毒肺炎中的作用及中医药调控机制研究进展

李俊杰; 李亚玲; 刘永琦; 张志明; 董娟娟; 李高勤; 刘东玲; 靳晓杰; 张利英

doi:10.13422/j.cnki.syfjx.20201907

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M1/M2型肺泡巨噬细胞亚群在新型冠状病毒肺炎中的作用及中医药调控机制研究进展

抗疫专题 | 更新时间：2020-09-16

- M1/M2型肺泡巨噬细胞亚群在新型冠状病毒肺炎中的作用及中医药调控机制研究进展
- Effect of M1/M2 Alveolar Macrophage Subsets in COVID-19 and Regulatory Mechanism of Traditional Chinese Medicine
- 中国实验方剂学杂志 2020年26卷第19期页码：99-107
- 作者机构：
  
  1.甘肃中医药大学甘肃省高校重大疾病分子医学与中医药防治研究省级重点实验室，兰州 730000
  2.甘肃中医药大学基础医学院，兰州 730000
  3.甘肃中医药大学附属医院，兰州 730000
- 作者简介：
  
  李俊杰，在读硕士，从事中医药防治肿瘤的研究，E-mail：15521269445@163.com
  刘永琦，博士，教授，博士生导师，从事中医药防治肿瘤的研究，E-mail：liuyongqi73@163.com
- 基金信息：
  
  2020年度甘肃省重大疾病分子医学与中医药防治研究重点实验室新型冠状病毒防治研究开放基金项目(FZYX20-2)
- DOI：10.13422/j.cnki.syfjx.20201907
  中图分类号： R2-0;R22;R285.5;R284
- 收稿日期：2020-05-26，
  
  网络出版日期：2020-07-21，
  
  纸质出版日期：2020-10-05
- 稿件说明：
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李俊杰,李亚玲,刘永琦等.M1/M2型肺泡巨噬细胞亚群在新型冠状病毒肺炎中的作用及中医药调控机制研究进展[J].中国实验方剂学杂志,2020,26(19):99-107.

LI Jun-jie,LI Ya-ling,LIU Yong-qi,et al.Effect of M1/M2 Alveolar Macrophage Subsets in COVID-19 and Regulatory Mechanism of Traditional Chinese Medicine[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(19):99-107.
李俊杰,李亚玲,刘永琦等.M1/M2型肺泡巨噬细胞亚群在新型冠状病毒肺炎中的作用及中医药调控机制研究进展[J].中国实验方剂学杂志,2020,26(19):99-107. DOI： 10.13422/j.cnki.syfjx.20201907.

LI Jun-jie,LI Ya-ling,LIU Yong-qi,et al.Effect of M1/M2 Alveolar Macrophage Subsets in COVID-19 and Regulatory Mechanism of Traditional Chinese Medicine[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(19):99-107. DOI： 10.13422/j.cnki.syfjx.20201907.

摘要

新型冠状病毒肺炎（COVID-19）死亡患者的病理解剖结果显示肺部过度的炎症反应是诱发急性肺损伤或急性呼吸窘迫综合征等并发症的重要原因之一，调节过度的免疫应答对治疗该病有重要的意义。肺泡巨噬细胞具有高度的异质性和可塑性，在机体感染早期和后期，M1/M2型肺泡巨噬细胞亚群平衡及功能的动态变化对肺部炎性反应具有显著的影响。本文综述巨噬细胞的分型及功能，探讨巨噬细胞在新冠肺炎不同阶段病理过程的作用机制以及中药治疗的药效机制，为中医药治疗新型冠状病毒肺炎以及基于调控巨噬细胞极化的药物研发上提供思路。

Abstract

The pathological anatomical results of coronavirus disease-2019 (COVID-19) patients showed that excessive inflammatory reaction in the lungs is one of the important causes for such complications as acute lung injury or acute respiratory distress syndrome. Therefore

regulation of immune response may be an effective measure for COVID-19. Alveolar macrophages have a high heterogeneity and plasticity. The dynamic changes of subsets balance and function of M1/M2 alveolar macrophages have a significant effect on pulmonary inflammatory response during the early and late stages of infection. This paper reviews the classification and function of macrophages and explores the mechanism of alveolar macrophage in the pathological process of COVID-19 at different stages and the pharmacodynamic mechanism of traditional Chinese medicine. Besides

it provides ideas for the treatment of COVID-19 with traditional Chinese medicine and other drugs' research and development based on the regulation of macrophage polarization.

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Keywords

references

VIJAYAN A , RUMBO M , CARNOY C , et al . Compartmentalized antimicrobial defenses in response to flagellin [J]. Trends Microbiol , 2018 , 26 ( 5 ): 423 - 435 .

ATRI C , GUERFALI F Z . Role of human macrophage polarization in inflammation during infectious diseases [J]. Int J Mol Sci , 2018 , doi: 10.3390/ijms19061801 http://dx.doi.org/10.3390/ijms19061801 .

VERRECK F A , DE BOER T , LANGENBERG D M , et al . Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria [J]. Proc Natl Acad Sci USA , 2004 , 101 ( 13 ): 4560 - 4565 .

HIGGINS D M , SANCHEZ-CAMPILLO J , ROSAS-TARACO A G , et al . Relative levels of M-CSF and GM-CSF influence the specific generation of macrophage populations during infection with Mycobacterium tuberculosis [J]. J Immunol , 2008 , 180 ( 7 ): 4892 - 4900 .

BHATIA M , ZEMANS R L , JEYASEELAN S . Role of chemokines in the pathogenesis of acute lung injury [J]. Am J Respir Cell Mol Biol , 2012 , 46 ( 5 ): 566 - 572 .

HUSSELL T , BELL T J . Alveolar macrophages:plasticity in a tissue-specific context [J]. Nat Rev Immunol , 2014 , 14 ( 2 ): 81 - 93 .

GORITZKA M , MAKRIS S , KAUSAR F , et al . Alveolar macrophage-derived type I interferons orchestrate innate immunity to RSV through recruitment of antiviral monocytes [J]. J Exp Med , 2015 , 212 ( 5 ): 699 - 714 .

SHIREY K A , LAI W , PLETNEVA L M , et al . Agents that increase AAM differentiation blunt RSV-mediated lung pathology [J]. J Leukoc Biol , 2014 , 96 ( 6 ): 951 - 955 .

SAVILL J . Recognition and phagocytosis of cells undergoing apoptosis [J]. Br Med Bull , 1997 , 53 ( 3 ): 491 - 508 .

ORTEGA-GOMEZ A , PERRETTI M , SOEHNLEIN O . Resolution of inflammation:an integrated view [J]. EMBO Mol Med , 2013 , 5 ( 5 ): 661 - 74 .

HOFFMANN P R , KENCH J A , VONDRACEK A , et al . Interaction between phosphatidylserine and the phosphatidylserine receptor inhibits immune responses in vivo [J]. J Immuno , 2005 , 174 ( 3 ): 1393 - 1404 .

HUYNH M L , FADOK V A , HENSON P M . Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation [J]. J Clin Invest , 2002 , 109 ( 1 ): 41 - 50 .

TIAN S , HU W , NIU L , et al . Pulmonary pathology of early phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer [J]. J Thorac Oncol , 2020 , 15 ( 5 ): 700 - 704 .

NICHOLLS J M , POON L L , LEE K C , et al . Lung pathology of fatal severe acute respiratory syndrome [J]. Lancet (London , England) , 2003 , 361 ( 9371 ): 1773 - 1778 .

ROBERTS A , DEMING D , PADDOCK C D , et al . A mouse-adapted SARS-coronavirus causes disease and mortality in BALB/c mice [J]. PLoS Pathogens , 2007 , 3 ( 1 ): e5 .

HUANG C , WANG Y , LI X , et al . Clinical features of patients infected with 2019 novel coronavirus in Wuhan,China [J]. Lancet (London , England) , 2020 , 395 ( 10223 ): 497 - 506 .

LAW H K , CHEUNG C Y , NG H Y , et al . Chemokine up-regulation in SARS-coronavirus-infected,monocyte-derived human dendritic cells [J]. Blood , 2005 , 106 ( 7 ): 2366 - 2374 .

伍冬冬 , 潘频华 , 覃庆武 . 急性肺损伤/急性呼吸窘迫综合征发病机制研究进展 [J]. 中华结核和呼吸杂志 , 2015 , 38 ( 7 ): 524 - 527 .

CHEN Y , ZHANG JJ , LIU Y , et al . Comprehensive comparison and analysis of the prevention and treatment of coronavirus disease 2019 and severe acute respiratory syndrome with traditional chinese medicine [J]. World J Tradit Chin Med , 2020 , 6 ( 2 ): 124 - 131 .

OUMOUNA M , WEITNAUER M , MIJOSEK V , et al . Cell-contact dependent inhibition of monocytes by airway epithelial cells and reversion by infection with respiratory syncytial virus [J]. Immunobiology , 2015 , 220 ( 11 ): 1240 - 1245 .

ITALIANI P , MAZZA E M , LUCCHESI D , et al . Transcriptomic profiling of the development of the inflammatory response in human monocytes in vitro [J]. PLoS One , 2014 , 9 ( 2 ): e87680 .

WRAPP D , WANG N . Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation [J]. Science , 2020 , 367 ( 6483 ): 1260 - 1263 .

XU H , ZHONG L , DENG J , et al . High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa [J]. Int J Oral Sci , 2020 , 12 ( 1 ): 8 .

YAO X H , LI T Y , HE Z C , et al . A pathological report of three COVID-19 cases by minimally invasive autopsies [J]. Chin J Pathol , 2020 , 49 : E009 .

QI F , QIAN S , ZHANG S , et al . Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses [J]. Biochem Biophys Res Commun , 2020 , doi: 10.1101/2020.02.16.951913 http://dx.doi.org/10.1101/2020.02.16.951913 .

CHANNAPPANAVAR R , PERLMAN S . Pathogenic human coronavirus infections:causes and consequences of cytokine storm and immunopathology [J]. Semin Immunopathol , 2017 , 39 ( 5 ): 529 - 539 .

REN Y , KHAN F A , PANDUPUSPITASARI N S , et al . Immune evasion strategies of pathogens in macrophages:the potential for limiting pathogen transmission [J]. Curr Issues Mol Biol , 2017 , 21 : 21 - 40 .

NIKITINA E , LARIONOVA I , CHOINZONOV E , et al . Monocytes and macrophages as viral targets and reservoirs [J]. Int J Mol Sci , 2018 , doi: 10.3390/ijms19092821 http://dx.doi.org/10.3390/ijms19092821 .

TASAKA S . Acute lung injury/acute respiratory distress syndrome:progress in diagnosis and treatment.topics:I.Pathogenesis and pathophysiology; 3.Pathogenesis and pathophysiology of ALI/ARDS [J]. Nihon Naika Gakkai Zasshi , 2011 , 100 ( 6 ): 1529 - 1535 .

DA SILVA-SANTOS J E , SANTOS-SILVA M C , CUNHA FDE Q , et al . The role of ATP-sensitive potassium channels in neutrophil migration and plasma exudation [J]. J Pharmacol Exp Ther , 2002 , 300 ( 3 ): 946 - 951 .

LIU L , WEI Q , LIN Q , et al . Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection [J]. JCI Insight , 2019 , 4 ( 4 ): e123158 .

PETERANDERL C , MORALES-NEBREDA L , SELVAKUMAR B , et al . Macrophage-epithelial paracrine crosstalk inhibits lung edema clearance during influenza infection [J]. J Clin Invest , 2016 , 126 ( 4 ): 1566 - 1580 .

NARASARAJU T , YANG E , SAMY R P , et al . Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis [J]. Am J Pathol , 2011 , 179 ( 1 ): 199 - 210 .

EYAL F G , HAMM C R , PARKER J C . Reduction in alveolar macrophages attenuates acute ventilator induced lung injury in rats [J]. Intensive Care Med , 2007 , 33 ( 7 ): 1212 - 1218 .

ALBER A , HOWIE S E , WALLACE W A , et al . The role of macrophages in healing the wounded lung [J]. Int J Exp Pathol , 2012 , 93 ( 4 ): 243 - 251 .

HE C , LARSON-CASEY J L , GU L , et al . Cu,Zn-superoxide dismutase-mediated redox regulation of Jumonji Domain containing 3 modulates macrophage polarization and pulmonary fibrosis [J]. Am J Respir Cell Mol Biol , 2016 , 55 ( 1 ): 58 - 71 .

WANG C Y , LU C Y , LI S W , et al . SARS coronavirus papain-like protease up-regulates the collagen expression through non-Samd TGF-beta1 signaling [J]. Virus Res , 2017 , 235 : 58 - 66 .

LIU S S , LV X X , LIU C , et al . Targeting degradation of the transcription factor C/EBpbeta reduces lung fibrosis by restoring activity of the ubiquitin-editing enzyme A20 in macrophages [J]. Immunity , 2019 , 51 ( 3 ): 522 - 534 .

JWANG J , XU L Z , XIANG Z , et al . Microcystin-LR ameliorates pulmonary fibrosis via modulating CD206 M2-like macrophage polarization [J]. Cell Death Dis , 2020 , 11 ( 2 ): 136 .

CASSOL E , CASSETTA L , RIZZI C , et al . M1 and M2a polarization of human monocyte-derived macrophages inhibits HIV-1 replication by distinct mechanisms [J]. J Immunol , 2009 , 182 ( 10 ): 6237 - 6246 .

刘永琦 . 系统生物学对中西医结合研究的影响 [J]. 中医杂志 , 2007 , 10 : 869 - 871,75 .

魏本君 , 王庆胜 , 雍文兴 , 等 . 甘肃新型冠状病毒肺炎特征及中医治疗 [J]. 中国中医药信息杂志 , 2020 , doi: 11.3519.R.20200225.1740.002 http://dx.doi.org/11.3519.R.20200225.1740.002 .

刘清泉 , 夏文广 , 安长青 , 等 . 中西医结合治疗新型冠状病毒肺炎作用的思考 [J]. 中医杂志 , 2020 , 61 ( 6 ): 463 - 464 .

路志正 , 路喜善 . “清肺排毒汤”彰显中医药抗疫疗效与自信 [J]. 中医杂志 , 2020 , doi: 11.2166.R.20200302.0930.002 http://dx.doi.org/11.2166.R.20200302.0930.002 .

徐天馥 , 贺成功 , 杨坤 . 基于网络药理学清肺排毒汤治疗新冠肺炎的物质基础及作用机制研究 [J]. 天然产物研究与开发 , 2020 , 32 : 901 - 908 .

彭修娟 , 杨新杰 , 许刚 , 等 . 基于整合药理学探讨清肺排毒汤治疗新型冠状病毒肺炎的功效及作用机制 [J]. 中国实验方剂学杂志 , 2020 , doi: 11.3495.R.20200514.1136.002 http://dx.doi.org/11.3495.R.20200514.1136.002 .

吴昊 , 王佳琪 , 杨雨薇 , 等 . 基于网络药理学和分子对接技术初步探索“清肺排毒汤”抗新型冠状病毒肺炎作用机制 [J]. 药学学报 , 2020 , dio: 10 . 16438 / j.0513-4870.2020-0136 .

任伟钰 , 苏敬 , 刘永琦 , 等 . 全国各省区中医药治疗新型冠状病毒肺炎（COVID-19）的诊疗方案分析 [J]. 中草药 , 2020 , doi: 10.7501/j.issn.0253-2670.2020.05.007 http://dx.doi.org/10.7501/j.issn.0253-2670.2020.05.007 .

钟晓琴 , 李冷 , 卢传坚 , 等 . 苦杏仁苷对脂多糖诱导的RAW264.7巨噬细胞炎症模型的影响 [J]. 中药新药与临床药理 , 2018 , 29 ( 3 ): 257 - 263 .

胡景新 , 孟凡会 , 苏畅 , 等 . 中药石膏对烧伤鼠血浆、脾组织、腹腔巨噬细胞中环核苷酸以及血浆PGE_2含量的影响 [J]. 中国病理生理杂志 , 1991 , 7 ( 1 ): 12 - 15 .

冯伟科 , 于华芸 , 王媛 , 等 . 小檗碱和大黄酸对LPS诱导巨噬细胞炎症反应及TLR2/NF- κ B信号通路的影响 [J]. 山东医药 , 2018 , 58 ( 42 ): 24 - 27 .

郭迎科 , 葛信艳 , 李瑞琴 , 等 . 瓜蒌薤白汤含药血清抗博来霉素诱导的大鼠肺泡巨噬细胞致纤维化作用及机制研究 [J]. 亚太传统医药 , 2018 , 14 ( 5 ): 9 - 12 .

金叶智 . 汉黄芩素对流感病毒感染肺泡巨噬细胞炎症物质的影响及机制 [D]. 北京 : 北京中医药大学 , 2011 .

TAN J , LI L , SHI W , et al . Protective effect of 2-hydroxymethyl anthraquinone from hedyotis diffusa willd in lipopolysaccharide-induced acute lung injury mediated by TLR4-NF-kappaB pathway [J]. Inflammation , 2018 , 41 ( 6 ): 2136 - 2148 .

祁建平 , 祁晓媛 , 王晓娟 . 不同剂量金花清感颗粒对流行性感冒的疗效及对患者血清细胞因子的影响 [J]. 现代医学 , 2016 , 44 ( 12 ): 1664 - 9166 .

李琦 , 尹婕 , 冉庆森 , 等 . 急性肺损伤模型中连花清瘟胶囊对巨噬细胞趋化能力的药效与机制研究 [J]. 中国中药杂志 , 2019 , 44 ( 11 ): 2317 - 2323 .

何子龙 , 方文娟 , 张方博 , 等 . 疏风解毒胶囊肠吸收液对LPS诱导巨噬细胞释放细胞因子的影响 [J]. 中国现代中药 , 2015 , 17 ( 4 ): 345 - 348 .

李玲 , 张波 , 卢芳国 , 等 . A型流感病毒对肺巨噬细胞自噬的影响及麻杏石甘汤含药血清的干预作用 [J]. 中国药理学通报 , 2019 , 35 ( 6 ): 878 - 884 .

邱馨仪 . 麻杏石甘汤抗甲Ⅰ型流感病毒FM1株的实验研究 [J]. 广州:广州中医药大学 , 2013 .

张云 , 杨卉 , 何轩辉 , 等 . 麻杏石甘汤治疗新冠肺炎细胞因子风暴的网络药理学分析 [J]. 世界中医药 , 2020 , doi: 11.5529.R.20200430.1033.002 http://dx.doi.org/11.5529.R.20200430.1033.002 .

LQ M , CS P , N Y , et al . Posttreatment with Ma-Xing-Shi-Gan-Tang,a Chinese medicine formula,ameliorates lipopolysaccharide-induced lung microvessel hyperpermeability and inflammatory reaction in rat [J]. Microcirculation , 2014 , 21 ( 7 ): 649 - 663 .

吴莹 , 金叶智 , 张舒 , 等 . 小檗碱对流感病毒感染肺泡巨噬细胞炎性细胞因子的影响及其分子机制研究 [J]. 中国免疫学杂志 , 2012 , 28 ( 2 ): 125 - 131 .

SAKAGUCHI S . Metabolic aspects of endotoxin as a model of septic shock-approached from oxidative stress [J]. Yakugaku Zasshi , 2004 , 124 ( 2 ): 69 - 87 .

YUAN Y P ， WANG Y P ， ZHAI H Q , et al . Effects of Mahuang(Herba Ephedra Sinica) and Wuweizi(Fructus Schisandrae Chinensis) medicated serum on chemotactic migration of alveolar macrophages and inters regions macrophages in rats [J]. J Trad Chin Med , 2017 , 37 ( 5 ): 607 - 615 .

SUMIKO H , MASASHI H , NAOHIRO O , et al . Ephedrine alkaloids-free Ephedra Herb extract:a safer alternative to ephedra with comparable analgesic,anticancer,and anti-influenza activities [J]. J Nat Med , 2016 , 70 ( 3 ): 571 - 583 .

CHIBUIKE C U , JAE-YOUNG J , YOUNG-SOOK C , et al . Almond protein hydrolysate fraction modulates the expression of proinflammatory cytokines and enzymes in activated macrophages [J]. Food Funct , 2013 , 4 ( 5 ): 777 - 783 .

ZHANG A , PAN W Y , LV J , et al . Protective effect of amygdalin on LPS-induced acute lung injury by inhibiting NF- κ B and NLRP3 signaling pathways [J]. Inflammation , 2017 , 40 ( 3 ): 745 - 751 .

HU B , ZHANG H , MENG H , et al . Aloe-emodin from rhubarb (Rheum rhabarbarum) inhibits lipopolysaccharide-induced inflammatory responses in RAW264.7 macrophages [J]. J Ethnopharmacol , 2014 , 153 ( 3 ): 846 - 853 .

LEE J S , LEE Y N , LEE Y T , et al . Ginseng protects against respiratory syncytial virus by modulating multiple immune cells and inhibiting viral replication [J]. Nutrients , 2015 , 7 ( 2 ): 1021 - 1036 .

BAO S , ZOU Y , WANG B , et al . Ginsenoside Rg1 improves lipopolysaccharide-induced acute lung injury by inhibiting inflammatory responses and modulating infiltration of M2 macrophages [J]. Int Immunopharmacol , 2015 , 28 ( 1 ): 429 - 434 .

MA Q H , REN M Y , LUO J B . San Wu Huangqin decoction regulates inflammation and immune dysfunction induced by influenza virus by regulating the NF- κ B signaling pathway in H1N1-infected mice [J]. J Ethnopharmacol , 2020 , doi: 10.1016/j.jep.2020.112800 http://dx.doi.org/10.1016/j.jep.2020.112800 .

CHEN J J , HUANG C C , CHANG H Y , et al . Scutellaria baicalensis ameliorates acute lung injury by suppressing inflammation in vitro and in vivo [J]. Am J Chin Med , 2017 , 45 ( 1 ): 137 - 157 .

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