This experimental study was aimed to investigate the effect of mitochondrial damage-associated molecular patterns on the lung fluid homeostasis in experimental acute lung injury. Samples of serum and bronchoalveolar lavage fluid were obtained from patients and control subjects. The mice were intratracheally injected with mitochondrial and lipopolysaccharide damage-associated molecular (MDAM) patterns. The mice alveolar epithelial type 2 cells were incubated with the mitochondrial damage-associated molecular patterns.
Patients were divided into indirect and direct (extrapulmonary and pulmonary) injury cohorts on the basis of etiology. The release of mitochondrial peptide NAD dehydrogenase-1 in both bronchoalveolar lavage fluid and serum was induced in patients and was associated with etiology. The proteomic analysis of mouse lung tissues revealed the involvement of tight junction proteins and ion channels 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.
In conclusion, the mitochondrial damage-associated molecular patterns are found to exacerbate lung fluid imbalance in the experimental lung injury model through the formyl peptide receptor-1 signaling. The inhibition of this signaling may prevent further exacerbation of lung fluid imbalance induced by mitochondrial damage-associated molecular patterns. Hence, formyl peptide receptor-1 is a potential therapeutic target for acute respiratory distress syndrome (ARDS).
