title: Deep vein thrombosis resolution is modulated by monocyte CXCR2-mediated activity in a mouse model.
abstract: OBJECTIVE
  To determine the role of CXCR2, the receptor for cysteine-X-cysteine (CXC) chemokines, and its primary effector cell, the neutrophil (PMN), on deep venous thrombosis (DVT) resolution.
  
  
  RESULTS
  DVT in BALB/c, anti-CXCR2 antibody-treated, and BALB/c CXCR2(-/-) mice were created by infrarenal inferior vena cava (IVC) ligation and the thrombus harvested at various time points over 21 days. The CXCR2(-/-) mice had significantly larger thrombi at early time points (days 2 to 8), and significantly decreased intrathrombus PMNs, monocytes, and neovascularization as compared with controls. Thrombus KC/CXCL1 was significantly higher at 2 days in CXCR2-/- thrombi as measured by enzyme-linked immunosorbent assay. Fibrin content was significantly higher, with less uPA gene expression at 4 days in CXCR2-/- thrombi. Late fibrotic maturation of the thrombus was delayed in the CXCR2-/- mice, with significantly decreased 8 day MMP-2 activity, whereas MMP-9 activity was elevated as compared with controls. Similar impairment in DVT resolution was found at 8 days with anti-CXCR2 inhibition. However, systemic neutropenia, unlike CXCR2 deletion, did not increase the thrombus size as compared with controls.
  
  
  CONCLUSIONS
  Normal DVT resolution involves CXCR2-mediated neovascularization, collagen turnover, and fibrinolysis, and it is probably primarily monocyte-dependent.
authors.affiliation: Section of Vascular Surgery, Jobst Vascular Research Laboratory, University of Michigan Medical School, Ann Arbor, Mich, USA. henke@umich.edu
authors.forename: Peter K
authors.initials: PK
authors.lastname: Henke
authors.forename: Andrea
authors.initials: A
authors.lastname: Varga
authors.forename: Sumit
authors.initials: S
authors.lastname: De
authors.forename: C Barry
authors.initials: CB
authors.lastname: Deatrick
authors.forename: Jonathon
authors.initials: J
authors.lastname: Eliason
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Arenberg
authors.forename: Pasu
authors.initials: P
authors.lastname: Sukheepod
authors.forename: Porama
authors.initials: P
authors.lastname: Thanaporn
authors.forename: Steven L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: Gilbert R
authors.initials: GR
authors.lastname: Upchurch
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Wakefield
mesh_terms: D000818:Animals; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000235:genetics; D002633:Chemotaxis; D003094:Collagen / Q000032:analysis; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005337:Fibrin / Q000032:analysis; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D007797:Laminin / Q000032:analysis; D008026:Ligation; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D023421:Models, Animal; D009000:Monocytes / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000209:etiology; D009503:Neutropenia / Q000150:complications; D009504:Neutrophils / Q000502:physiology; D023063:Receptors, Interleukin-8B / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D014682:Vena Cava, Inferior; D020246:Venous Thrombosis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D007797:Laminin; D023063:Receptors, Interleukin-8B; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D005337:Fibrin; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9