血小板的穿透式電子顯微鏡影像：正常情況（左圖）；膿毒症導致炎症細胞 死亡（右圖）。 相片來源： Nature Cardiovascular Research (2022), 1(8), 732–747 。 Transmission electron microscopy images of platelets under normal conditions (left) and during sepsis (right), showing platelets undergoing inflammatory cell death. Source: Adapted from Nature Cardiovascular Research (2022), 1(8), 732–747.
Zooming in on platelet cells
To address these challenges, the HKMU team is investigating whether platelets could serve as early indicators of disease severity. “If there are objective biomarkers that could help detect the disease at an early stage, doctors could act sooner, rather than relying on the more obvious signs that appear only at a later stage when sepsis turns severe,” Prof. Tang explains. While platelets are best known for blood clotting, Prof. Tang’s research focuses on their active role in the immune response, which can become harmful in sepsis. Their reaction can cause abnormal clotting, excessive inflammation and a sharp drop in platelet numbers, all of which can contribute to organ failure. The team’s research focuses on PANoptosis, a newly recognised form of inflammatory cell death that combines three self-destruct mechanisms, known as pyroptosis, apoptosis and necroptosis, into a single coordinated process that can have harmful effects. Preliminary findings show that PANoptosis occurs in platelets during sepsis, and the team is now examining the mechanism by which this process contributes to uncontrolled inflammation and disordered clotting. Using cell culture studies and mouse models, the HKMU team is collaborating with Prof. Jack Wong Wing-tak, from the School of Life Sciences at The Chinese University of Hong Kong, on this three-year project.
聚焦血小板
都大團隊正研究血小板能否用作判斷病情輕重的早期指標。鄧教授解 釋：「若能找到客觀的生物標記，就有助在早期識別膿毒症患者，讓醫 生及早診斷，而非依靠在病情嚴重時才出現的明顯症狀。」 血小板最為人熟知的是其凝血功能，但鄧教授的研究發現，它們在激發 免疫反應中亦扮演重要角色。這些免疫反應可能危害膿毒症患者的性 命，引發凝血異常、過度炎症，以及血小板數量急劇下降，最終導致器 官衰竭。 都大團隊現正聚焦研究「泛凋亡」，這是近年發現的一種炎症細胞死亡 過程。它將三種細胞自毀機制，分別為焦亡、凋亡和壞死性細胞死亡， 結合為單一且協調的過程並同時發生，從而引發免疫系統出現上述問 題。團隊的初步研究結果顯示，膿毒症患者的血小板會出現泛凋亡。團 隊亦正深入研究此過程導致炎症失控和凝血異常的調控機制。
就這個為期三年的項目，都大團隊正與香港中文大學生命科學學院黃永 德教授合作，利用細胞培養和小鼠模型進行研究。
Finding biomarkers for a test kit
尋找生物標記以研發試劑
Building on the findings, the team is working to identify protein biomarkers that could signal PANoptosis at an early stage. One promising candidate is gasdermin D (GSDMD), which may serve as an early warning sign of excessive immune activation. The team is also studying another candidate, S100A8/A9, to understand how it may be uniquely activated during sepsis. These candidates could be potential biomarkers for the early diagnosis of severe sepsis, enabling more timely treatment. They may also represent potential therapeutic targets for alternative treatment strategies. “We aim to identify more proteins and translate the findings of the current research into a simple test kit that requires only a few drops of blood, enabling quicker assessment in clinical settings,” adds Prof. Tang. “By better understanding the molecular pathways involved in the body’s response to sepsis through this project, we can incorporate more protein candidates into the test kit to improve its accuracy.”
基於上述發現，都大團隊正尋找相關蛋白生物標記，以便及早偵測細胞 泛凋亡。團隊鎖定其中一個具潛力的蛋白生物標記—— GSDMD ，可被 視作免疫系統過度激活的早期警號；同時團隊亦正審視 S100A8/A9 ，了 解它在膿毒症中獨特的激活機制。這兩種蛋白有望成為早期診斷嚴重膿 毒症的生物標記，讓病人得到及時治療，亦可用作研發替代療法的靶 點。 鄧教授補充：「我們的目標是找出更多與膿毒症相關的蛋白，繼而研發 快速檢測工具，只需數滴血液便可完成檢測，讓醫生更快作出臨床評 估。透過這項研究，我們將可更深入理解身體對膿毒症的分子調控機 制，從而把更多相關的蛋白生物標記納入檢測試劑中，進一步提升檢測 的準確度。」
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