TY - JOUR
T1 - Monocyte recruitment in venous thrombus resolution
AU - Ali, Tahir
AU - Humphries, Julia
AU - Burnand, Kevin
AU - Sawyer, Barbara
AU - Bursill, Christina
AU - Channon, Keith
AU - Greaves, David
AU - Rollins, Barrett
AU - Charo, Israel F.
AU - Smith, Alberto
N1 - Funding Information:
T. A. was funded by a Clinical Research Fellowship from the Guy’s & St Thomas’ Charitable Foundation. J. H. was funded by the British Heart Foundation. I. F. C. is supported by National Institutes of Health grants HL52773 and HL063894.
PY - 2006/3
Y1 - 2006/3
N2 - Objective: 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. Methods: 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. Results: 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. Conclusion: 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.
AB - Objective: 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. Methods: 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. Results: 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. Conclusion: 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.
UR - http://www.scopus.com/inward/record.url?scp=33644669438&partnerID=8YFLogxK
U2 - 10.1016/j.jvs.2005.10.073
DO - 10.1016/j.jvs.2005.10.073
M3 - Article
C2 - 16520180
AN - SCOPUS:33644669438
SN - 0741-5214
VL - 43
SP - 601
EP - 608
JO - Journal of Vascular Surgery
JF - Journal of Vascular Surgery
IS - 3
ER -