中国输血杂志2026，Vol.39Issue(6)：711-717,7.DOI:10.13303/j.cjbt.issn.1004-549x.2026.06.002
Syk对CD36抗体介导血小板减少的调控作用分析
Analysis of the regulatory effect of Syk on CD36 antibody-mediated thrombocytopenia
摘要
Abstract
Objective To investigate the molecular mechanism of Syk in phagocytosis induced by CD36 antibodies.Methods In vitro,two CD36 monoclonal antibodies,GZ1(IgG2a)and GZ4(IgG1),at different concentrations were co-incubated with platelets from CD36-positive blood donors,and the affinity of the antibodies for platelets was assessed using flow cytometry.CD36 positive platelets from donors were labeled with Red-SE.The GZ1 and GZ4 antibodies were added to-gether with dye-labeled platelets to peripheral blood from blood donors for phagocytosis experiments.The expression of the Spleen Tyrosine Kinase(Syk),P-Syk,P38 MAPK and P-P38 were detected using Western blot(WB).In the in vitro phagocytosis inhibition assay,Fcγ receptor(FcγR)antibodies or Syk inhibitor(R406)were pre-incubated with monocytes prior to performing the phagocytosis experiment.In vivo experiments were performed using female C57BL/6J mice.R406 was administered via intraperitoneal injection,followed by tail vein infusion of GZ1 or GZ4 antibodies.Additionally,a treat-ment group was set up in which the antibodies were infused first,followed by administration of R406.Changes in platelet counts were analyzed using a blood routine analyzer,and antibody binding to platelets was detected by flow cytometry.Re-sults GZ1 had higher affinity for CD36positive platelets than GZ4.The phagocytosis rate induced by GZ1 was significantly higher than that of GZ4[(42.12±2.25)%vs(16.25±6.45)%,P<0.001].Moreover,GZ1-mediated platelet phagocyto-sis mainly depends on FcγRⅠ of monocytes,while GZ4-mediated platelet phagocytosis mainly relies on FcγRⅡof mono-cytes.WB results showed that the GZ1 group significantly upregulated the expression of Syk and phosphorylated Syk(P-Syk),and induced phosphorylation of the downstream P38 MAPK signaling pathway.Pretreatment of monocytes with R406 inhibited the phagocytosis of antibodyopsonized platelets by monocytes.After injecting GZ1 or GZ4 antibodies into C57BL/6 female mice through the tail vein,GZ1 mAbs had a stronger binding rate to the platelets compared with GZ4 mAbs,lead-ing to a significant decrease in platelet count.After pre-injecting R406 into mice,the platelet count reduction in both the GZ1 and GZ4 groups was alleviated,and the binding rate of antibodies to platelets was also significantly reduced.However,administration of R406 after antibody injection failed to prevent the decrease in platelet counts in mice.Conclusion This study indicates that Syk plays an important role in the phagocytosis of anti-CD36 opsonized platelets by monocytes/macro-phages and is closely associated with the activation of the P38 MAPK signaling pathway.关键词
CD36/血小板减少症/抗体依赖性细胞吞噬作用(ADCP)/Fc 依赖性吞噬作用/脾酪氨酸激酶(Syk)Key words
CD36/thrombocytopenia/antibody-dependent cellular phagocytosis(ADCP)/Fc dependent phagocytosis/spleen tyrosine kinase(Syk)分类
医药卫生引用本文复制引用
任慧,陈大伟,罗亚林,夏文杰,叶欣,何坚森,许耀日,徐秀章,付涌水..Syk对CD36抗体介导血小板减少的调控作用分析[J].中国输血杂志,2026,39(6):711-717,7.基金项目
国家自然科学基金项目(82270237、82470231) （82270237、82470231）
广州市科技计划项目(20241A011068、2024A03J0079) （20241A011068、2024A03J0079）
广州市市校(院)企联合资助专题(2025A03J3367、2025A03J3369) （院）
广州市医学重点学科(2025-2027) （2025-2027）
广东省基础与应用基础研究基金项目(2025A1515010465) （2025A1515010465）
