Attenuation of transfusion-related acute lung injury by FAK inhibitor PF-562271

Abstract

Background Transfusion-related acute lung injury (TRALI) is a specific form of acute lung injury (ALI) that can cause complications such as respiratory distress, hypoxia, fever, and tachycardia in patients. In some cases, symptoms can develop within 6 h of a transfusion, and chest X-rays may reveal bilateral lung opacity. A study using mice found that the focal adhesion kinase (FAK) inhibitor PF-562271 improved ALI. Methods For the study, male BALB/Cmice aged 6–8 weeks were randomly assigned to four groups: a blank control group, a group injected with lipopolysaccharide (LPS), a group injected with LPS and 5-day stored platelets (TRALI mouse model), and a group treated with the FAK inhibitor. Pathological changes in the lung tissue, lung wet/dry weight ratio, myeloperoxidase (MPO) activity, and the expression of TNF-α, IL-6, IL-8, and FAK protein were analyzed to determine the effects of the FAK inhibitor 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 model group. The lung wet/dry weight ratio confirmed that the pulmonary edema induced by the model group was more severe than that of the LPS group. MPO activity was higher in the TRALI group than in the LPS group. The mRNA expression of TNF-α, IL-6, IL-8, and the protein expression of FAK in the lung tissue were up-regulated. After 24 h of FAK inhibitor intervention, the pulmonary edema in TRALI mice was significantly reduced, the infiltration of inflammatory cells in lung tissue was improved, the lung function was better, and the expression of inflammatory factors was downregulated. Conclusions The study successfully constructed a mouse TRALI model infused with aged platelets and found that the FAK inhibitor can alleviate the lung injury caused by TRALI and increase the survival rate of TRALI. Therefore, FAK inhibitors may have potential applications in the treatment of TRALI.