Tirofiban interferes with antibody-mediated transfusion-related acute lung injury by inhibiting platelet-neutrophil binding
10.13303/j.cjbt.issn.1004-549x.2022.04.006
- VernacularTitle:替罗非班抑制血小板与中性粒细胞结合干预抗体介导小鼠输血相关急性肺损伤
- Author:
Xin YUAN
1
;
Yunhong YU
1
;
Congchao QIAO
1
;
Pan SUN
1
;
Na SU
1
;
Peng JIANG
1
;
Fangzhao LIN
1
Author Information
1. Institute of Blood Transfusion, Chinese Academy of Medical Science& Peking Union Medical College, Chengdu 610052, China
- Publication Type:Journal Article
- Keywords:
transfusion-related acute lung injury (TRALI);
aggregate, platelet-neutrophil;
GP Ⅱ b/Ⅲa receptor antagonist;
tirofiban
- From:
Chinese Journal of Blood Transfusion
2022;35(4):377-382
- CountryChina
- Language:Chinese
-
Abstract:
【Objective】 To explore the feasibility of tirofiban, a platelet surface glycoprotein (GP)Ⅱb/Ⅲa receptor antagonist intervene in transfusion-related acute lung injury (TRALI), by inhibiting platelet activation and by preventing platelet and neutrophil binding to form aggregates. 【Methods】 1) Fifty wild-type male Balb/c mice, aged 8 to 10 weeks, were randomly divided into TRALI, normal, tirofiban TRALI intervention, isotype control and tirofiban normal intervention groups. In the TRALI model, tirofiban TRALI intervention and isotype control groups, each mouse was injected intraperitoneally with lipopolysaccharide (LPS) 0.1 mg/kg, and after 18 h with 4.5 mg/kg anti-MHC-I or IgG2a isotype control antibody, in which 0.5 μg/g tirofiban was injected 30 min before anti-MHC-I injection, and was labeled as tirofiban TRALI intervention. The group without any treatment was set as normal group. The tirofiban normal intervention group was injected with only 0.5 μg/g tirofiban into the tail vein, 30 min before the injection of anti-MHC-I. 2) After antibody injection, the mice were observed for 2 h, then executed with their lungs removed, and the extent of lung injury and the intervention effect of tirofiban were analyzed by comparing the differences in lung dry to wet ratio, total protein, myeloperoxidase (MPO), inflammatory factors and quantitative results of HE staining. The platelet activation level in whole blood and immunofluorescence (IF) quantification of platelet and neutrophil fluorescence were detected by flow cytometry to analyze the mechanism of tirofiban on TRALI. 【Results】 1) The indexes of lung injury in the tirofiban TRALI intervention group and TRALI model group for HE staining were 0.663 3±0.141 9 vs. 0.173 3±0.120 4 (P<0.05), respectively; 2) Platelet activation levels(%)in whole blood in the TRALI group, normal group and tirofiban TRALI intervention group were 22.87±9.943 vs 5.070±2.234 vs 5.767±3.224(P<0.05), respectively. 3) The mean fluorescence density of platelet neutrophil aggregates for IF detection in the tirofiban intervention group and TRALI model group was 21.89±3.536 vs. 32.77±0.9624 (P<0.05). 【Conclusion】 The platelet GP Ⅱ b/Ⅲa-specific inhibitor tirofiban inhibited platelet-neutrophil binding in mice, thus could possibly intervene in TRALI.
