Nanoscale platelet extracellular vesicles mediate inflammatory lung injury through Cd36–Fyn-dependent macrophage polarization in transfusion-related acute lung injuryOA
Platelet-derived extracellular vesicles(pEVs)are abundant nanoscale bioeffectors released during platelet storage,yet their functional roles in transfusion-associated complications remain largely unexplored.The present study demonstrates that pEVs act as potent nanocarriers that aggravate transfusion-related acute lung injury(TRALI)through activation of the Cd36–Fyn signaling pathway in macrophages.Integrated single-cell RNA sequencing and mechanistic analyses demonstrated that pEVs administration selectively induced M1 macrophage polarization and amplified pulmonary inflammation.Cd36 was markedly upregulated in the Fn1^(+)macrophage subset,serving as the receptor that mediates pEV uptake and Fyn activation.Molecular and pharmacological inhibition of Cd36–Fyn signaling significantly attenuated pro-inflammatory cytokine expression,lung tissue damage,and mortality in vivo.These findings elucidate how nanoscale platelet vesicles reprogram macrophage responses and disrupt immune homeostasis,providing a mechanistic framework for understanding TRALI progression.Identification of the Cd36–Fyn axis as a molecular link between nanovesicle signaling and immune dysregulation highlights new therapeutic opportunities for transfusion safety and nanomedicine-based interventions.
Chenggao Wu;Jiamei Hu;Wei Liu;Linju Kuang;Yize Wu;Aiping Le
Department of Transfusion Medicine,Key Laboratory of Jiangxi Province for Transfusion Medicine,The First Affiliated Hospital,Jiangxi Medical College,Nanchang University,Nanchang 330006,ChinaThe Center of Breast Professional Disease Diagnosis and Treatment,The First Affiliated Hospital,Jiangxi Medical College,Nanchang University,Nanchang 330006,ChinaDepartment of Transfusion Medicine,Key Laboratory of Jiangxi Province for Transfusion Medicine,The First Affiliated Hospital,Jiangxi Medical College,Nanchang University,Nanchang 330006,ChinaDepartment of Transfusion Medicine,Key Laboratory of Jiangxi Province for Transfusion Medicine,The First Affiliated Hospital,Jiangxi Medical College,Nanchang University,Nanchang 330006,ChinaDepartment of Transfusion Medicine,Key Laboratory of Jiangxi Province for Transfusion Medicine,The First Affiliated Hospital,Jiangxi Medical College,Nanchang University,Nanchang 330006,ChinaDepartment of Transfusion Medicine,Key Laboratory of Jiangxi Province for Transfusion Medicine,The First Affiliated Hospital,Jiangxi Medical College,Nanchang University,Nanchang 330006,China
医药卫生
transfusion-related acute lung injuryplatelet-derived extracellular vesiclesM1 macrophagesCd36–Fyn pathwaytherapeutic strategy
《Nano Research》 2026 (5)
P.840-857,18
supported by Natural Science Foundation Program of Jiangxi Province(Nos.20232BAB216040 and 20252BAC240526)the National Natural Science Foundation of China(Nos.82560048 and 82472225)Science and Technique Point Program of Department of Education of Jiangxi Province(No.GJJ210112)Science and technology innovation base plan of Jiangxi Province-Key Laboratory of Jiangxi Province for Transfusion Medicine(No.2024SSY06171)。
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