Paraquat is a herbicide that produces a well-characterized model of acute oxidant lung injury through generation of reactive oxygen species and epithelial damage. The mannose receptor CD206 is expressed on macrophages and implicated in modulation of macrophage phenotype and tissue responses, but its role during chemically induced oxidant lung injury has not been fully defined. This study compared outcomes after paraquat exposure in C57BL/6J wild-type mice and mice genetically deficient in CD206 to determine whether CD206 influences mortality, inflammation, tissue injury, and macrophage-associated epithelial protection.
The investigators used C57BL/6J wild-type and CD206-deficient mice exposed to paraquat to induce acute lung injury. Endpoints included survival, body weight change, bronchoalveolar lavage (BAL) measures, histological assessment of lung injury and fibrosis, quantification of oxidative DNA damage via 8-OHdG, and expression analysis of cytoprotective genes in alveolar macrophages (notably Hmox1). Parallel in vitro co-culture experiments were performed using monocyte-derived macrophages from the two genotypes and airway epithelial cells to test macrophage-dependent effects on epithelial viability, and the antioxidant N-acetylcysteine (NAC) was used to probe redox-dependent mechanisms.
Key experimental outcomes reported in the source were:
After paraquat exposure, mice lacking CD206 experienced worse outcomes compared with wild-type controls. Specifically, CD206-deficient animals had increased mortality and greater loss of body weight. Bronchoalveolar lavage revealed elevated protein and increased total cell counts in CD206-deficient mice, indicating more pronounced barrier disruption and inflammation. Histological assessment showed higher fibrosis scores in the lungs of CD206-deficient mice, consistent with aggravated structural injury after oxidant challenge.
Markers of oxidative damage were increased in the absence of CD206: levels of the oxidative DNA adduct 8-OHdG were higher in CD206-deficient lungs after paraquat. Concurrently, alveolar macrophages from CD206-deficient mice displayed reduced expression of Hmox1, a gene encoding heme oxygenase-1 with known antioxidant and cytoprotective functions. These observations link CD206 deficiency to impaired macrophage antioxidant responses and increased oxidative injury in the lung following paraquat exposure.
In co-culture assays, monocyte-derived macrophages from CD206-deficient mice increased epithelial cell death relative to macrophages from wild-type mice, demonstrating a macrophage-dependent effect on epithelial viability. Addition of the antioxidant N-acetylcysteine restored epithelial survival in co-cultures containing CD206-deficient macrophages, supporting the interpretation that enhanced epithelial injury was mediated at least in part by redox-dependent mechanisms tied to the lack of CD206.
The data identify a previously unrecognized protective role for CD206 in macrophage-associated epithelial defense during acute oxidant lung injury induced by paraquat. CD206 deficiency was associated with increased mortality, worsened alveolar-capillary leakage and inflammation, greater histological fibrosis, elevated oxidative DNA damage (8-OHdG), and diminished macrophage Hmox1 expression. Functional co-culture studies implicate macrophage-driven oxidative mechanisms in epithelial injury that can be reversed by the antioxidant N-acetylcysteine.
These findings suggest that CD206 contributes to macrophage-mediated cytoprotection in the setting of chemical oxidant injury, potentially via regulation of antioxidant pathways such as Hmox1. While the study used a paraquat model in mice and did not report clinical treatment recommendations, the results provide a basis for further mechanistic work on macrophage lectin receptors in oxidant lung injury and raise the possibility that enhancing macrophage antioxidant responses could mitigate epithelial damage in similar contexts.
The authors declared no known competing financial interests or personal relationships that could have influenced the work. The study is reported in Biochemical and Biophysical Research Communications (2026) with PubMed ID 42365825 and DOI 10.1016/j.bbrc.2026.154208. The source states the primary keywords as Acute lung injury; CD206; Macrophage; Oxidative stress.
Note: Specific numerical values (e.g., exact survival rates, quantitative fold-changes, p values) and detailed experimental protocols were not provided in the abstract section of the source and therefore are not reported here.