objective: To investigate the effect of mitochondrial damage-associated molecular patterns on the lung fluid homeostasis in experimental acute lung injury.
methods: Experimental study.
methods: Research laboratory.
methods: Patients with acute respiratory distress syndrome and control subjects, wild-type C57BL/6 and formyl peptide receptor-1 gene knockout mice, and primary rat alveolar epithelial type II cells.
methods: Samples of bronchoalveolar lavage fluid and serum were obtained from patients and control subjects. Mice were intratracheally instilled with lipopolysaccharide and mitochondrial damage-associated molecular patterns. The primary rat alveolar epithelial type II cells were isolated and incubated wi... More
objective: To investigate the effect of mitochondrial damage-associated molecular patterns on the lung fluid homeostasis in experimental acute lung injury.
methods: Experimental study.
methods: Research laboratory.
methods: Patients with acute respiratory distress syndrome and control subjects, wild-type C57BL/6 and formyl peptide receptor-1 gene knockout mice, and primary rat alveolar epithelial type II cells.
methods: Samples of bronchoalveolar lavage fluid and serum were obtained from patients and control subjects. Mice were intratracheally instilled with lipopolysaccharide and mitochondrial damage-associated molecular patterns. The primary rat alveolar epithelial type II cells were isolated and incubated with mitochondrial damage-associated molecular patterns.
results: Patients were divided into direct (pulmonary) and indirect (extrapulmonary) injury groups based on etiology. The release of mitochondrial peptide nicotinamide adenine dinucleotide dehydrogenase 1 in both bronchoalveolar lavage fluid and serum was induced in patients and was associated with etiology. In the lipopolysaccharide-induced lung injury, administration of mitochondrial damage-associated molecular patterns exacerbated the lung fluid imbalance, which was mitigated in formyl peptide receptor-1 knockout mice. Proteomic analysis of mouse lung tissues revealed the involvement of ion channels and tight junction proteins in this process. Treatment with mitochondrial damage-associated molecular patterns decreased the expression of epithelial sodium channel α, zonula occludens-1, and occludin via the formyl peptide receptor-1/p38 pathway in the primary rat alveolar epithelial type II cells.
conclusions: Mitochondrial damage-associated molecular patterns exacerbate lung fluid imbalance in the experimental acute lung injury model through formyl peptide receptor-1 signaling, the inhibition of which may prevent exacerbation of lung fluid imbalance induced by mitochondrial damage-associated molecular patterns. Thus, formyl peptide receptor-1 is a potential therapeutic target for acute respiratory distress syndrome.
