Ali Tahir, Humphries Julia, Burnand Kevin, Sawyer Barbara, Bursill Christina, Channon Keith, Greaves David, Rollins Barrett, Charo Israel F, Smith Alberto
Academic Department of Surgery, Cardiovascular Division, GKT, King's College, St Thomas's Hospital, London, United Kingdom.
J Vasc Surg. 2006 Mar;43(3):601-8. doi: 10.1016/j.jvs.2005.10.073.
To investigate the importance of monocyte recruitment in thrombus resolution and the role of cysteine-cysteine (CC) chemokines and the CC chemokine receptor, CCR2, in this process.
Peritoneal macrophages, monocyte chemotactic protein 1 (MCP1), or carrier solutions were injected into thrombi induced in the vena cava of rats. Caval thrombi were also formed in CCR2-/- and MCP1-/- mice and in wild-type mice transfected with an adenoviral construct expressing a broad-spectrum CC receptor antagonist.
Direct administration of peritoneal macrophages decreased thrombus size by more than fivefold and increased recanalization by more than fourfold compared with controls (P < .001). A 100-ng MCP1dose reduced thrombus size by more than sixfold (P < .01) and increased recanalization by more than sevenfold (P < .01), without affecting macrophage recruitment. Deletion of CCR2 or blockade of all CC chemokines inhibited both monocyte recruitment (P < .05) and thrombus resolution (P < .01), but knocking out MCP-1 had no effect.
Increasing macrophage numbers in the thrombus enhances its resolution. MCP1 treatment enhances resolution by stimulating recanalization, independent of an effect on monocyte recruitment. CCR2 deficiency has the same effect as blockade of all CC chemokines. CCR2 receptor activation may therefore be an important mechanism in monocyte recruitment into venous thrombi and could be targeted to promote their resolution.
研究单核细胞募集在血栓溶解中的重要性以及半胱氨酸-半胱氨酸（CC）趋化因子和CC趋化因子受体CCR2在此过程中的作用。
将腹腔巨噬细胞、单核细胞趋化蛋白1（MCP1）或载体溶液注入大鼠腔静脉诱导形成的血栓中。还在CCR2基因敲除小鼠、MCP1基因敲除小鼠以及用表达广谱CC受体拮抗剂的腺病毒构建体转染的野生型小鼠中形成腔静脉血栓。
与对照组相比，直接注射腹腔巨噬细胞可使血栓大小减小超过五倍，再通率提高超过四倍（P <.001）。100 ng的MCP1剂量可使血栓大小减小超过六倍（P <.01），再通率提高超过七倍（P <.01），且不影响巨噬细胞募集。CCR2基因缺失或所有CC趋化因子的阻断均抑制单核细胞募集（P <.05）和血栓溶解（P <.01），但敲除MCP-1则无影响。
增加血栓中的巨噬细胞数量可增强其溶解。MCP1治疗通过刺激再通来增强溶解，而与对单核细胞募集的影响无关。CCR2缺陷与所有CC趋化因子的阻断具有相同的效果。因此，CCR2受体激活可能是单核细胞募集到静脉血栓中的重要机制，并且可以作为促进血栓溶解的靶点。
