日前,，國際權威期刊《血液》（Blood）刊登了來自哈佛醫(yī)學院史家嵐研究團隊的最新研究成果"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細胞白血?。ˋPL）細胞的促凝和纖溶活性,，乳粘素和吞噬可以協(xié)同改善APL中的凝血紊亂,。
APL是以危及生命的血栓和出血以及早幼粒細胞的積聚為特征的疾病,，盡管這種疾病代表了一種成功治療的范例,，在臨床和實驗水平皆取得了明顯的進步，但APL細胞的移除過程仍有待研究,。特別是在化療后，損傷的腫瘤細胞的命運和這些細胞在哪里和怎樣被清除還不清楚,，延遲排除這些細胞將直接導致彌漫性血管內凝血及隨后的出血,，故治療早期死亡率高,。
急性早幼粒細胞白血病凝血紊亂主要與APL原始細胞的促凝物質和纖溶激活物相關，但是這些白血病細胞的宿命仍不清楚,。在這項研究中,，我們探究了MΦ和Ecs在體外對APL細胞的吞噬作用以及其與APL促凝活性和纖溶活性的相關性。另外科學家研究了乳粘素在吞噬中的作用,，并確定了乳粘素和吞噬具有協(xié)同調節(jié)APL凝血功能紊亂的作用,。結果顯示：培養(yǎng)的MΦ和Ecs都能吞噬APL細胞，乳粘素以時間依賴性的方式促進了這種吞食,。
總之,，研究證明了MΦ和ECs在體外對APL細胞的吞噬作用能夠防止APL的凝血紊亂，乳粘素通過其促進吞食APL細胞的作用或許可以用于減少白血病細胞數量,，乳粘素和巨噬細胞具有能夠協(xié)同降低凝血活性的能力,，其對PS相關的凝血功能紊亂有可能是一個有吸引力的治療策略。并且,，乳粘素介導的吞食將有助于改善APL纖溶亢進狀態(tài),。（生物谷bioon.com）
相關閱讀：
PNAS：一基因調控或可抑制白血病細胞惡性增殖
Science：砒霜治療APL分子機制新成果
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.
