日前，国际权威期刊《血液》（Blood）刊登了来自哈佛医学院史家岚研究团队的最新研究成果"Phagocytosis by macrophages and endothelial cells inhibits procoagulant and fibrinolytic activity of acute promyelocytic leukemia cells"。研究成果表明吞噬抑制了急性早幼粒细胞白血病（APL）细胞的促凝和纤溶活性，乳粘素和吞噬可以协同改善APL中的凝血紊乱。
APL是以危及生命的血栓和出血以及早幼粒细胞的积聚为特征的疾病，尽管这种疾病代表了一种成功治疗的范例，在临床和实验水平皆取得了明显的进步，但APL细胞的移除过程仍有待研究。特别是在化疗后，损伤的肿瘤细胞的命运和这些细胞在哪里和怎样被清除还不清楚，延迟排除这些细胞将直接导致弥漫性血管内凝血及随后的出血，故治疗早期死亡率高。
急性早幼粒细胞白血病凝血紊乱主要与APL原始细胞的促凝物质和纤溶激活物相关，但是这些白血病细胞的宿命仍不清楚。在这项研究中，我们探究了MΦ和Ecs在体外对APL细胞的吞噬作用以及其与APL促凝活性和纤溶活性的相关性。另外科学家研究了乳粘素在吞噬中的作用，并确定了乳粘素和吞噬具有协同调节APL凝血功能紊乱的作用。结果显示：培养的MΦ和Ecs都能吞噬APL细胞，乳粘素以时间依赖性的方式促进了这种吞食。
总之，研究证明了MΦ和ECs在体外对APL细胞的吞噬作用能够防止APL的凝血紊乱，乳粘素通过其促进吞食APL细胞的作用或许可以用于减少白血病细胞数量，乳粘素和巨噬细胞具有能够协同降低凝血活性的能力，其对PS相关的凝血功能紊乱有可能是一个有吸引力的治疗策略。并且，乳粘素介导的吞食将有助于改善APL纤溶亢进状态。（生物谷bioon.com）
相关阅读：
PNAS：一基因调控或可抑制白血病细胞恶性增殖
Science：砒霜治疗APL分子机制新成果
doi:10.1182/blood-2011-06-362186
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Phagocytosis by macrophages and endothelial cells inhibits procoagulant and fibrinolytic activity of acute promyelocytic leukemia cells
Rui Xie1, Chunyan Gao1, Wen Li1, Jiuxin Zhu1, Valerie Novakovic2, Jing Wang1, Ruishuang Ma1, Jin Zhou1, Gary E. Gilbert2, and Jialan Shi2,*
The coagulopathy of acute promyelocytic leukemia (APL) is mainly related to procoagulant substances and fibrinolytic activators of APL blasts, but the fate of these leukemic cells is unknown. The aim of this study was to investigate the removal of APL blasts by macrophages and endothelial cells in vitro and consequent procoagulant and fibrinolytic activity of APL cells. We found that human umbilical vein endothelial cells as well as THP-1 and monocyte-derived macrophages bound, engulfed and subsequently degraded immortalized APL cell line NB4 and primary APL cells. Lactadherin promoted phagocytosis of APL cells in a time-dependent fashion. Furthermore, factor Xa and prothrombinase activity of PS-exposed target APL cells was time-dependently decreased after incubation with phagocytes (THP-1-derived macrophages or human umbilical vein endothelial cells). Thrombin production on target APL cells was reduced by 40-45% after two hours of coincubation with phagocytes, and 80% by a combination of lactadherin and phagocytes. Moreover, plasmin generation of target APL cells was inhibited 30% by two hours of phagocytosis, and approximately 50% by lactadherin-mediated engulfment. These results suggest that engulfment by macrophages and endothelial cells reduce procoagulant and fibrinolytic activity of APL blasts. Lactadherin and phagocytosis could cooperatively ameliorate the clotting disorders in APL.
