Ficolin A derived from local macrophages and neutrophils protects against lipopolysaccharide-induced acute lung injury by activating complement.

Abstract

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.

• Authors: Xu Wu, Duoduo Yao, Linlin Bao, Di Liu, Xiaoxue Xu, Yunqing An, Xulong Zhang, Bin Cao
• Journal: Immunology and cell biology (Immunol Cell Biol) Vol. 98 Issue 7 Pg. 595-606 (08 2020) ISSN: 1440-1711 [Electronic] United States
• PMID: 32339310 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 Australian and New Zealand Society for Immunology Inc.

Chemical References

• Lectins
• Lipopolysaccharides
• Complement System Proteins

Topics

• Acute Lung Injury (chemically induced, immunology)
• Animals
• Complement System Proteins (immunology)
• Lectins (immunology)
• Lipopolysaccharides
• Macrophages (immunology)
• Mice
• Mice, Knockout
• Neutrophils (immunology)
• Ficolins