Attenuation of Transfusion-Related Acute Lung Injury by FAK Inhibitor PF-562271

Abstract

Background: Transfusion-related acute lung injury (TRALI) is a form of acute lung injury (ALI) that can cause complications such as respiratory distress, hypoxia, fever, and tachycardia in patients. A study using mice found that the focal adhesion kinase (FAK) inhibitor PF-562271 improved ALI. This study aimed to investigate whether PF-562271 could inhibit the progression of inflammation in a mouse model of TRALI. Methods: Platelets were collected from experimental mice and stored for 5 days. The mice were injected intraperitoneally with lipopolysaccharide (LPS), and then the stored platelets were injected into the mice through the tail vein to establish the TRALI model. Lung tissue samples were collected from the mice after the experiment. Pathological changes in the lung tissue, lung wet/dry weight ratio, myeloperoxidase (MPO) activity, and the expression of Tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6), Interleukin-8 (IL-8), and FAK protein were analyzed to determine the effects of PF-562271 on TRALI in mice. Results: Histological analysis revealed that the alveolar interstitium was filled with inflammatory cells and the alveolar septum was significantly widened in the TRALI model group. The lung wet/dry weight ratio confirmed that the pulmonary edema induced in the TRALI group was more severe than that in the LPS group (p < 0.001). MPO activity was higher in the TRALI group than in the LPS group (p < 0.001). The mRNA expression of TNF-α, IL-6, and IL-8, and protein expression of FAK in the lung tissue were up-regulated (p < 0.05, p < 0.01, p < 0.001). After 24 h of FAK inhibitor intervention, the pulmonary edema in TRALI mice was significantly reduced, the infiltration of inflammatory cells in the lung tissue was improved, the lung function was better, and the expression of inflammatory factors was downregulated (p < 0.05, p < 0.01, p < 0.001). Conclusions: We successfully constructed a mouse TRALI model infused with aged platelets and found that the FAK inhibitor PF-562271 could alleviate the lung injury caused by TRALI and increase the survival rate of TRALI mice. Therefore, FAK inhibitors may have potential applications in the treatment of TRALI.