LAUSR

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 ficolins knockout mouse model by CRISPR/Cas9 technology, and used flow cytometry and hematoxylin & eosin staining to study the expressions and roles of local ficolins in LPS-induced pulmonary inflammation and injury. Our results found that besides ficolin B, ficolin A 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 ficolin A and ficolin B, and T and B cells also express a small amount of ficolin B. The intranasal administration of LPS induced local pulmonary inflammation with the increased recruitment of macrophages and neutrophils. LPS stimulation induced increased expression of ficolin A and ficolin B 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 via 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 ficolin A protects against LPS-induced acute lung injury by mediating extracellular complement activation.