中山大学学报（医学科学版）2025，Vol.46Issue(6)：1006-1014,9.
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
The Role of Complement in MHC Class Ⅰ Antibody-mediated Transfusion-related Acute Lung Injury
摘要
Abstract
[Objective]Transfusion-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.[Methods]This 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.[Results]Mice 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.[Conclusion]Complement 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.关键词
输血相关急性肺损伤/MHC-Ⅰ类抗体/补体/补体C5a受体/膜攻击复合物/细胞因子Key words
transfusion-related acute lung injury/MHC-Ⅰ antibody/complement/complement C5a receptor/membrane attack complex/cytokines分类
医药卫生引用本文复制引用
张泽,陈大伟,何坚森,叶汉深,付涌水..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[J].中山大学学报（医学科学版）,2025,46(6):1006-1014,9.基金项目
国家自然科学基金(82470231) （82470231）
广东省基础与应用基础研究基金(2023A1515010924,2025A1515010465,2024A1515013071) （2023A1515010924,2025A1515010465,2024A1515013071）
广州市科技计划项目校企联合资助专题(2025A03J3453,2025A03J3369) （2025A03J3453,2025A03J3369）
广州市医学重点学科(2025-2027年)项目(SYCZZX252402) （2025-2027年）
