Demers Melanie, Wagner Denisa D
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts.
Semin Thromb Hemost. 2014 Apr;40(3):277-83. doi: 10.1055/s-0034-1370765. Epub 2014 Mar 3.
Neutrophils have long been known as innate immune cells that phagocytose and kill pathogens and mount inflammatory responses protecting the host from infection. In the past decades, new aspects of neutrophils have emerged unmasking their importance not only in inflammation but also in many pathological conditions including thrombosis and cancer. The 2004 discovery that neutrophils, upon strong activation, release decondensed chromatin to form neutrophil extracellular traps (NETs), has unveiled new avenues of research. Here, we review current knowledge regarding NETs in thrombosis, with a special focus on cancer-associated thrombosis as well as their potential role in cancer growth and metastasis. We discuss the prospective use of NET-specific biomarkers, such as citrullinated histone H3 and NET inhibitors, as tools to anticipate and fight cancer-associated thrombosis. We propose that the rapid developments in the field of NETosis may provide new targets to combat the thrombotic consequences of cancer and perhaps even help to contain the disease itself.
长期以来,中性粒细胞一直被认为是一种先天性免疫细胞,能够吞噬和杀死病原体,并引发炎症反应以保护宿主免受感染。在过去几十年中,中性粒细胞的新特性不断涌现,揭示了它们不仅在炎症中,而且在包括血栓形成和癌症在内的许多病理状况中都具有重要作用。2004年发现中性粒细胞在强烈激活时会释放解聚的染色质以形成中性粒细胞胞外陷阱(NETs),这开辟了新的研究途径。在此,我们综述了关于NETs在血栓形成方面的现有知识,特别关注癌症相关血栓形成以及它们在癌症生长和转移中的潜在作用。我们讨论了NET特异性生物标志物(如瓜氨酸化组蛋白H3)和NET抑制剂作为预测和对抗癌症相关血栓形成工具的前瞻性用途。我们认为,NETosis领域的快速发展可能为对抗癌症的血栓形成后果提供新的靶点,甚至可能有助于控制疾病本身。