Ficolin A derived from local macrophages and neutrophils protects against lipopolysaccharide‐induced acute lung injury by activating complement,Immunology and Cell Biology

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Ficolin A derived from local macrophages and neutrophils protects against lipopolysaccharide‐induced acute lung injury by activating complement
Immunology and Cell Biology ( IF 3.2 ) Pub Date : 2020-04-27 , DOI: 10.1111/imcb.12344
Xu Wu ₁ , Duoduo Yao ₂ , Linlin Bao ₃ , Di Liu ₄ , Xiaoxue Xu ₅ , Yunqing An ₂ , Xulong Zhang ₂ , Bin Cao _{1,

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Affiliation

Ficolins are important and widely distributed pattern recognition molecules that can induce lectin complement pathway activation and initiate the innate immune response. Although ficolins can bind lipopolysaccharide (LPS) in vitro , the sources, dynamic changes and roles of local ficolins in LPS‐induced pulmonary inflammation and injury remain poorly understood. In this study, we established a ficolin knockout mouse model by clustered regularly interspaced short palindromic repeats/CRISPR‐associated protein 9 (CRISPR/Cas9) technology, and used flow cytometry and hematoxylin and eosin staining to study the expressions and roles of local ficolins in LPS‐induced pulmonary inflammation and injury. Our results show that besides ficolin B (FcnB), ficolin A (FcnA) is also expressed in leukocytes from the bone marrow, peripheral blood, lung and spleen. Further analyses showed that macrophages and neutrophils are the main sources of FcnA and FcnB, and T and B cells also express a small amount of FcnB. The intranasal administration of LPS induced local pulmonary inflammation with the increased recruitment of macrophages and neutrophils. LPS stimulation induced increased expression of FcnA and FcnB in neutrophils at the acute stage and in macrophages at the late stage. The severity of the lung injury and local inflammation of Fcna^−/− mice was increased by the induction of extracellular complement activation. The recovery of LPS‐induced local lung inflammation and injury was delayed in Fcnb^−/− mice. Hence, these findings suggested that the local macrophage‐ and neutrophil‐derived FcnA protects against LPS‐induced acute lung injury by mediating extracellular complement activation.

中文翻译：

来源于局部巨噬细胞和中性粒细胞的Ficolin A通过激活补体来预防脂多糖诱导的急性肺损伤

纤维蛋白是重要且分布广泛的模式识别分子，可以诱导凝集素补体途径激活并启动先天免疫应答。尽管ficolins可以在体外结合脂多糖（LPS），关于脂蛋白在LPS诱导的肺部炎症和损伤中的来源，动态变化和作用仍然知之甚少。在这项研究中，我们通过聚类的规则间隔的短回文重复序列/ CRISPR相关蛋白9（CRISPR / Cas9）技术建立了ficolin基因敲除小鼠模型，并使用流式细胞仪和苏木精和曙红染色研究了局部纤维蛋白在细胞中的表达和作用。 LPS引起的肺部炎症和损伤。我们的结果表明，除纤维胶凝蛋白B（FcnB）外，纤维胶凝蛋白A（FcnA）在骨髓，外周血，肺和脾脏的白细胞中也有表达。进一步的分析表明巨噬细胞和嗜中性粒细胞是FcnA和FcnB的主要来源，T细胞和B细胞也表达少量FcnB。鼻内给予LPS会引起局部肺部炎症，巨噬细胞和中性粒细胞的募集增加。LPS刺激诱导急性期中性粒细胞和晚期巨噬细胞中FcnA和FcnB的表达增加。肺损伤的严重程度和局部炎症Fcna ^-/- 小鼠通过诱导细胞外补体激活而增加。Fcnb ^-/- 小鼠延迟了LPS诱导的局部肺部炎症和损伤的恢复。因此，这些发现表明，局部巨噬细胞和嗜中性粒细胞衍生的FcnA通过介导细胞外补体激活来防止LPS诱导的急性肺损伤。

更新日期：2020-04-27

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