title: IL-6 mobilizes bone marrow-derived cells to the vascular wall, resulting in neointima formation via inflammatory effects.
abstract: OBJECTIVE
  Among the many factors related to bone marrow cell mobilization, local inflammation induced by cytokines may drive bone marrow cells to the vascular wall, resulting in a thickened neointima. However, the relationship between inflammatory reactions and bone marrow cell invasion has not yet been fully clarified.
  
  
  METHODS
  We inserted a large wire into the femoral artery in male balb/c(WT), interleukin (IL)-6-knockout (KO) and bone marrow-transplanted (BMT) mice that had received bone marrow cells from KO mice. Immunohistochemistry was performed to evaluate the degree of intimal hyperplasia and inflammation following vascular injury.
  
  
  RESULTS
  Three days after the vascular injury, the number of CD34/Sca-1-positive cells in the blood was higher in the KO mice. The numbers of apoptotic cells in the neointima was lower in the KO and BMT mice at two hours after injury. The morphometric analysis performed at one and four weeks after injury showed that the intima/media ratio was significantly lower in the KO and BMT mice, while CD34-positive cells were much more frequent in the WT mice. Furthermore, re-endothelialization appeared earlier in the KO and BMT mice than in the WT mice. No differences in the levels of vascular endothelial growth factor or hepatocyte growth factor were observed in the mice sera between the WT, KO and BMT mice after injury. The in vitro culture of bone marrow cells showed more differentiated smooth muscle-like cells in the WT mice than in the KO mice.
  
  
  CONCLUSIONS
  IL-6 is involved in neointimal formation following vascular injury, possibly acting through inflammatory effects inducing the production of bone marrow cells.
authors.affiliation: Department of Medicine, Division of Cardiology, Showa University School of Medicine.
authors.forename: Makoto
authors.initials: M
authors.lastname: Shoji
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Furuyama
authors.forename: Yuya
authors.initials: Y
authors.lastname: Yokota
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Omori
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Sato
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Tsunoda
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iso
authors.forename: Shinji
authors.initials: S
authors.lastname: Koba
authors.forename: Eiichi
authors.initials: E
authors.lastname: Geshi
authors.forename: Takashi
authors.initials: T
authors.lastname: Katagiri
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Youichi
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D004730:Endothelium, Vascular / Q000378:metabolism; D005434:Flow Cytometry; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007249:Inflammation / Q000473:pathology; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D058426:Neointima / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; C553307:HGF protein, mouse; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D017228:Hepatocyte Growth Factor