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rIL ‐35 prevents murine transfusion‐related acute lung injury by inhibiting the activation of endothelial cells
Author(s) -
Qiao Jiajia,
He Rui,
Yin Yonghua,
Tian Li,
Li Ling,
Lian Zhengqiu,
Fang Peng,
Liu Zhong
Publication year - 2020
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.15805
Subject(s) - medicine , lung , transfusion related acute lung injury , in vivo , pulmonary edema , endothelial stem cell , immunology , flow cytometry , in vitro , cytokine , lipopolysaccharide , antibody , pharmacology , biology , microbiology and biotechnology , biochemistry
BACKGROUND Transfusion‐related acute lung injury (TRALI) is an important cause of death associated with transfusion, and no specific clinical treatments are available. Endothelial cells are believed to play an important role in the development of TRALI. This study investigated whether IL‐35, an endothelial stabilizing cytokine could regulate the severity of antibody‐mediated TRALI in vivo. STUDY DESIGN AND METHODS Human microvascular endothelial cells (HMVECs) were cultured in vitro, rIL‐35(2 μg/mL) was added before HMVECs activation, and HMVECs were fully activated by LPS (0.5 μg/mL). Then cells were collected for flow cytometry analysis. We used a previously established “two‐event” mouse model of TRALI with naive and lipopolysaccharide (LPS)‐injected mice as controls. rIL‐35(100 μg/kg) was injected into the tail vein for 3 consecutive days before the induction of the TRALI model. Samples were collected 2 hours after TRALI induction and tested for lung tissue myeloperoxidase activity, total protein levels, lung tissue histology, endothelial cell activation assay, and cytokine assay. RESULTS In vitro culture of HMVECs with rIL‐35 verified that rIL‐35 inhibited endothelial cells. In a mouse model, prophylactic administration of rIL‐35 prevented pulmonary edema, increased lung protein levels, and reduced polymorphonuclear neutrophil accumulation in the lung. CONCLUSIONS This work suggests that antibody‐mediated murine TRALI can be prevented by rIL‐35, and that rIL‐35 appears to work by inhibiting the activation of lung endothelial cells.