Abstract
Background
Transfusion-related acute lung injury (TRALI) is the infusion of blood or blood system.
Objective
To explore the mechanism of TLR4-mediated T cell immune effect in TRALI.
Methods
In this animal study, a mouse model of LPS-induced TRALI was established. Sixty adult
C57/BL6 mice (wild-type, WT) were randomly divided into 5 groups: 1) normal WT type,
2) LPS control group of WT type lipopolysaccharide, 3) WT type TRALI group (LPS + MHC-I
mAb), 4) (TLR4 antibody) lipopolysaccharide LPS control group, 5) (TLR4 antibody)
TRALI group (LPS + MHC-I mAb). Mice were injected with LPS (0.1 mg/kg) and MHC-I mAb
(2 mg/kg) into the tail vein. H&E staining was performed to detect pathological features.
The myeloperoxidase (MPO) activity and the level of inflammatory cytokines in lung
tissue homogenate supernatant were measured. Blood, spleen single-cell suspension,
and bronchoalveolar lavage fluid were collected to detect the ratio of Treg and Th17
cells by flow cytometry. RT-PCR and WB were used to detect mRNA or protein expression.
Results
TLR4 mAb treatment alleviated the pathogenesis of LPS-induced TRALI in vivo, the MPO
activity, and the level of proinflammatory factors in lung tissues. TLR4 exerted its
function by changing of Treg/Th17 ratio via the SLIT2/ROBO4 signaling pathway and
downregulating CDH5 and SETSIP.
Conclusion
TLR4 mediates immune response in the LPS-induced TRALI model through the SLIT2/ROBO4
signaling pathway.
Abbreviations:
TRALI (Transfusion-related acute lung injury), MPO (myeloperoxidase), BALF (bronchoalveolar lavage fluid), ALI (acute lung injury), ROS (reactive oxygen species), ELISA (Enzyme-linked immunosorbent assay), MyD88 (myeloid differentiation factor 88), TRIF (domain-containing adaptor inducing IFN-B), Tram (TRIF-related adaptor molecule), Sarm (sterile and HEAT-Armadillo motifs-containing protein)Keywords
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Article Info
Publication History
Published online: July 07, 2022
Accepted:
July 4,
2022
Received in revised form:
June 29,
2022
Received:
April 25,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier Ltd. All rights reserved.
