Pulmonary coagulation and fibrinolysis abnormalities that favor fibrin deposition in the lungs of mouse antibody-mediated transfusion-related acute lung injury

Yu,Yunhong; Jiang,Peng; Sun,Pan; Su,Na; Lin,Fangzhao

doi:10.3892/mmr.2021.12239

Pulmonary coagulation and fibrinolysis abnormalities that favor fibrin deposition in the lungs of mouse antibody-mediated transfusion-related acute lung injury

Authors:
- Yunhong Yu
- Peng Jiang
- Pan Sun
- Na Su
- Fangzhao Lin
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Affiliations: Institute of Blood Transfusion, Chinese Academy of Medical Science and Peking Union Medical College, Chengdu, Sichuan 610052, P.R. China
Published online on: June 23, 2021 https://doi.org/10.3892/mmr.2021.12239
Article Number: 601
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Transfusion‑related acute lung injury (TRALI) is a life‑threatening disease caused by blood transfusion. However, its pathogenesis is poorly understood and specific therapies are not available. Experimental and clinical studies have indicated that alveolar fibrin deposition serves a pathological role in acute lung injuries. The present study investigated whether pulmonary fibrin deposition occurs in a TRALI mouse model and the possible mechanisms underlying this deposition. The TRALI model was established by priming male Balb/c mice with lipopolysaccharide (LPS) 18 h prior to injection of an anti‑major histocompatibility complex class I (MHC‑I) antibody. Untreated mice and mice administered LPS plus isotype antibody served as controls. At 2 h after TRALI induction, blood and lung tissue were collected. Disease characteristics were assessed based on lung tissue histology, inflammatory responses and alterations in the alveolar‑capillary barrier. Immunofluorescence staining was used to detect pulmonary fibrin deposition, platelets and fibrin‑platelet interactions. Levels of plasminogen activator inhibitor‑1 (PAI‑1), thrombin‑antithrombin complex (TATc), tissue factor pathway inhibitor (TFPI), coagulation factor activity and fibrin degradation product (FDP) in lung tissue homogenates were measured. Severe lung injury, increased inflammatory responses and a damaged alveolar‑capillary barrier in the LPS‑primed, anti‑MHC‑I antibody‑administered mice indicated that the TRALI model was successfully established. Fibrin deposition, fibrin‑platelet interactions and platelets accumulation in the lungs of mouse models were clearly promoted. Additionally, levels of TATc, coagulation factor V (FV), TFPI and PAI‑1 were elevated, whereas FDP level was decreased in TRALI mice. In conclusion, both impaired fibrinolysis and enhanced coagulation, which might be induced by boosted FV activity, increased pulmonary platelets accumulation and enhanced fibrin‑platelet interactions and contributed to pulmonary fibrin deposition in TRALI mice. The results provided a therapeutic rationale to target abnormalities in either coagulation or fibrinolysis pathways for antibody‑mediated TRALI.

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