Ficolin aggravates lipopolysaccharide-induced acute lung injury by regulating polarization of M1 macrophages

doi:10.3969/j.issn.1006-7795.2023.02.003

Abstract

Abstract:

Objective To investigate the effect and mechanisms of ficolin (Fcn) in acute lung injury induced by lipopolysaccharide (LPS) stimulation. Methods SPF C57BL/6 mice and ficolin gene knockout mice were randomly divided into 6 groups：WT-PBS group， WT-LPS group， Fcna^－/－-PBS group， Fcna^－/－-LPS group， Fcnb^－/－-PBS group and Fcnb^－/－-LPS group, according to the experimental requirements. Acute lung injury model was established after intranasal inoculation with 5 mg/kg LPS for 2 days. H&E staining was used to detect pathological damage of lung tissue. Flow cytometry was used to detect the proportions of neutrophils and macrophages in lung tissue. Western blotting was used to detect the expression of inducible nitric oxide synthase (iNOS) in lung tissue. Bone marrow derived macrophages in wild-type and ficolin knockout mice were isolated and cultured in vitro. After LPS stimulation, the expression of iNOS in cells and the concentration of nitric oxide (NO) in supernatant were detected. Results A mouse model of acute lung injury induced by intranasal inoculation of LPS was successfully established. LPS stimulation aggravated lung pathological injury, with increased pulmonary alveolar fusion and many inflammatory cells infiltration. Besides, the proportions of neutrophils and interstitial macrophages were significantly increased. The expression of iNOS and the production of NO in mouse lung tissue and bone marrow derived macrophages were significantly increased after LPS stimulation in vivo and in vitro. However, knockout of ficolin significantly reduced the recruitment of interstitial macrophages after LPS stimulation. Furthermore, knockout of ficolin ameliorated LPS induced acute lung injury, with reduced iNOS expression and NO production. Conclusion Ficolin can aggravate LPS induced acute lung injury by promoting polarization of M1 macrophages, which may be a potential therapeutic target for acute lung injury.

Key words: ficolin, lipopolysaccharide, acute lung injury, macrophage, inducible nitric oxide synthase

CLC Number:

R563

Li Yanxiu, Xu Zhixuan, Kong Qingli, Zhou Yujie, Zhang Xulong. Ficolin aggravates lipopolysaccharide-induced acute lung injury by regulating polarization of M1 macrophages[J]. Journal of Capital Medical University, 2023, 44(2): 196-202.

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URL: https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/10.3969/j.issn.1006-7795.2023.02.003

https://journal03.magtech.org.cn/Jweb_sdykdxxb/EN/Y2023/V44/I2/196

References

［1］Neupane A S, Willson M, Chojnacki A K, et al. Patrolling alveolar macrophages conceal bacteria from the immune system to maintain homeostasis［J］. Cell, 2020, 183(1):110－125.e11.
［2］Kumar V. Pulmonary innate immune response determines the outcome of inflammation during pneumonia and sepsis-associated acute lung injury［J］. Front Immunol, 2020, 11: 1722.
［3］Hughes K T, Beasley M B. Pulmonary manifestations of acute lung injury: more than just diffuse alveolar damage［J］. Arch Pathol Lab Med, 2017, 141(7):916－922.
［4］Mokra D, Mikolka P, Kosutova P, et al. Corticosteroids in acute lung injury: the dilemma continues［J］. Int J Mol Sci, 2019, 20(19):4765.
［5］Vichare R, Janjic J M. Macrophage-targeted nanomedicines for ARDS/ALI: promise and potential［J］. Inflammation, 2022, 45(6):2124－2141.
［6］Thompson B T, Chambers R C, Liu K D. Acute respiratory distress syndrome［J］. N Engl J Med, 2017, 377(6):562－572.
［7］Li N, Wang W, Jiang W Y, et al. Cytosolic DNA-STING-NLRP3 axis is involved in murine acute lung injury induced by lipopolysaccharide［J］. Clin Transl Med, 2020, 10(7):e228.
［8］Li J C, Lu K M, Sun F L, et al. Panaxydol attenuates ferroptosis against LPS-induced acute lung injury in mice by Keap1-Nrf2/HO-1 pathway［J］. J Transl Med, 2021, 19(1):96.
［9］Chen X X, Tang J, Shuai W Z, et al. Macrophage polarization and its role in the pathogenesis of acute lung injury/acute respiratory distress syndrome［J］. Inflamm Res, 2020, 69(9):883－895.
［10］S′wierzko A S, Cedzyński M. The influence of the lectin pathway of complement activation on infections of the respiratory system［J］. Front Immunol, 2020, 11: 585243.
［11］Matsushita M. Ficolins in complement activation［J］. Mol Immunol, 2013, 55(1):22－26.
［12］Kjaer T R, Hansen A G, Srensen U B S, et al. M-ficolin binds selectively to the capsular polysaccharides of Streptococcus pneumoniae serotypes 19B and 19C and of a Streptococcus mitis strain［J］. Infect Immun, 2013, 81(2):425－429.
［13］Ren Y S, Ding Q Q, Zhang X L. Ficolins and infectious diseases［J］. Virol Sin, 2014, 29(1):25－32.
［14］Lo M W, Kemper C, Woodruff T M. COVID-19: complement, coagulation, and collateral damage［J］. J Immunol, 2020, 205(6):1488－1495.
［15］Wu X, Bao L L, Hu Z Q, et al. Ficolin A exacerbates severe H1N1 influenza virus infection-induced acute lung immunopathological injury via excessive complement activation［J］. Cell Mol Immunol, 2021, 18(9):2278－2280.
［16］胡子琪, 吴旭, 姚朵朵, 等. Ficolin通过激活补体加重poly(I:C)联合LPS诱导的急性肺脏损伤［J］. 中国免疫学杂志, 2022, 38(14):1665－1670.
［17］Wu X, Yao D D, Bao L L, et al. Ficolin A derived from local macrophages and neutrophils protects against lipopolysaccharide-induced acute lung injury by activating complement［J］. Immunol Cell Biol, 2020, 98(7):595－606.
［18］Jin C, Chen J, Gu J, et al. Gut-lymph-lung pathway mediates sepsis-induced acute lung injury［J］. Chin Med J (Engl), 2020, 133(18):2212－2218.
［19］Long M E, Mallampalli R K, Horowitz J C. Pathogenesis of pneumonia and acute lung injury［J］. Clin Sci (Lond), 2022, 136(10):747－769.
［20］Jarlhelt I, Genster N, Kirketerp-Mller N, et al. The ficolin response to LPS challenge in mice［J］. Mol Immunol, 2019, 108: 121－127.
［21］Matsushita M. Ficolins: complement-activating lectins involved in innate immunity［J］. J Innate Immun, 2010, 2(1):24－32.
［22］Aoyagi Y, Adderson E E, Rubens C E, et al. L-ficolin/mannose-binding lectin-associated serine protease complexes bind to group B streptococci primarily through N-acetylneuraminic acid of capsular polysaccharide and activate the complement pathway［J］. Infect Immun, 2008, 76(1):179－188.
［23］Zhang J, Yang L F, Ang Z W, et al. Secreted M-ficolin anchors onto monocyte transmembrane G protein-coupled receptor 43 and cross talks with plasma C-reactive protein to mediate immune signaling and regulate host defense［J］. J Immunol, 2010, 185(11):6899－6910.
［24］Chen Y N, Hu M R, Wang L, et al. Macrophage M1/M2 polarization［J］. Eur J Pharmacol, 2020, 877: 173090.
［25］Anavi S, Tirosh O. iNOS as a metabolic enzyme under stress conditions［J］. Free Radic Biol Med, 2020, 146: 16－35.

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