The Role of Complement in MHC Class I Antibody-mediated Transfusion-related Acute Lung Injury
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2025.0610
- VernacularTitle:补体在主要组织相容性抗原Ⅰ类抗体介导的输血相关急性肺损伤中的作用
- Author:
Ze ZHANG
1
;
Dawei CHEN
2
;
Jiansen HE
2
;
Hanshen YE
3
;
Yongshui FU
1
Author Information
1. Nanfang Hospital， Southern Medical University， Guangzhou 510515， China
2. Institute of Blood Transfusion， Guangzhou Blood Centre， Guangzhou 510095， China
3. Guangdong Provincial People's Hospital Affiliated to Southern Medical University，Guangzhou 510080， China
- Publication Type:Journal Article
- Keywords:
transfusion-related acute lung injury;
MHC-Ⅰ antibody;
complement;
complement C5a receptor;
membrane attack complex;
cytokines
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2025;46(6):1006-1014
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTransfusion-Related Acute Lung Injury （TRALI） is a common fatal transfusion adverse reaction. Major Histocompatibility Complex （MHC） class I is an important factor involved in the pathogenesis of TRALI； however， the role of complement in itspathogenesis has not been fully elucidated. This study aims to explore the role of complement in MHC class I antibody-mediated TRALI， so as to provide a theoretical basis for clinical prevention and treatment. MethodsThis study established a murine model of transfusion-related acute lung injury （TRALI） based on the "two-hit" theory， with lipopolysaccharide （LPS） as the first hit and MHC class I antibody as the second hit. Male Balb/c mice were randomly divided into seven groups （n=5 per group per experiment）： Naive （blank control）， LPS （first hit only）， Isotype （isotype antibody control）， TRALI （model group）， C5aR1 inhi （C5aR1 antagonist intervention）， C5aR2 inhi （C5aR2 antagonist intervention）， and Anti-C5 （anti-complement C5 antibody intervention）. Rectal temperature was monitored after MHC class I antibody injection. After sample collection， the severity of pulmonary edema was assessed by measuring the lung wet-to-dry weight ratio， histological analysis， and immunohistochemistry. Serum and bronchoalveolar lavage fluid were collected to measure cytokine and complement levels. ResultsMice in the TRALI group exhibited a significant decrease in rectal temperature， an increased lung wet-to-dry weight ratio， elevated serum cytokine levels， and markedly heightened complement C5a levels in bronchoalveolar lavage fluid （P＜0.000 1）. Histopathological examination revealed substantial infiltration of inflammatory cells， predominantly neutrophils accompanied by fewer lymphocytes， plasma cells， and monocytes， along with increased deposition of the membrane attack complex C5b-9 in lung tissues. In contrast， mice treated with anti-C5 antibody demonstrated no significant decrease in rectal temperature. The lung wet-to-dry weight ratio in this group showed no statistical difference compared to either the Naive or Isotype control groups （P＞0.05）. Furthermore， these mice displayed reduced serum cytokine levels， a significant attenuation of inflammatory cell infiltration in the lungs， and a 100% survival rate at the 2-hour time point. However， mice administered either the C5aR1 antagonist or the C5aR2 antagonist failed to be protected and subsequently developed TRALI. ConclusionComplement activation， which forms the membrane attack complex C5b-9， plays a critical role in MHC class I antibody-mediated TRALI. Blocking complement C5 activation can effectively prevent the occurrence of TRALI.
