title: Chemokine (C-C motif) receptor 2 mediates mast cell migration to abdominal aortic aneurysm lesions in mice.
abstract: OBJECTIVE
  Mast cells participate importantly in abdominal aortic aneurysms (AAAs) by releasing inflammatory cytokines to promote vascular cell protease expression and arterial wall remodelling. Mast cells accumulate in AAA lesions during disease progression, but the exact chemokines by which mast cells migrate to the site of vascular inflammation remain unknown. This study tested the hypothesis that mast cells use chemokine (C-C motif) receptor 2 (CCR2) for their accumulation in experimental mouse AAA lesions.
  
  
  RESULTS
  We generated mast cell and apolipoprotein E double-deficient (Apoe(-/-)Kit(W-sh/W-sh)) mice and found that they were protected from angiotensin II (Ang II) chronic infusion-induced AAAs compared with Apoe(-/-) littermates. Using bone-marrow derived mast cells (BMMC) from Apoe(-/-) mice and CCR2 double-deficient (Apoe(-/-)Ccr2(-/-)) mice, we demonstrated that Apoe(-/-)Kit(W-sh/W-sh) mice receiving BMMC from Apoe(-/-)Ccr2(-/-) mice, but not those from Apoe(-/-) mice, remained protected from AAA formation. Adoptive transfer of BMMC from Apoe(-/-) mice into Apoe(-/-)Kit(W-sh/W-sh) mice also increased lesion content of macrophages, T cells, and MHC class II-positive cells; there was also increased apoptosis, angiogenesis, cell proliferation, elastin fragmentation, and medial smooth muscle cell loss. In contrast, adoptive transfer of BMMC from Apoe(-/-)Ccr2(-/-) mice into Apoe(-/-)Kit(W-sh/W-sh) mice did not affect these variables.
  
  
  CONCLUSIONS
  The increased AAA formation and associated lesion characteristics in Apoe(-/-)Kit(W-sh/W-sh) mice after receiving BMMC from Apoe(-/-) mice, but not from Apoe(-/-)Ccr2(-/-) mice, suggests that mast cells use CCR2 as the chemokine receptor for their recruitment in Ang II-induced mouse AAA lesions.
authors.affiliation: Department of Medicine,  Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115,  USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Huimei
authors.initials: H
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Jiusong
authors.initials: J
authors.lastname: Sun
authors.forename: Michael A
authors.initials: MA
authors.lastname: Shi
authors.forename: Galina K
authors.initials: GK
authors.lastname: Sukhova
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Shi
mesh_terms: D019264:Adoptive Transfer; D000804:Angiotensin II; D000818:Animals; D001012:Aorta, Abdominal / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000473:pathology; D009389:Neovascularization, Pathologic; D019009:Proto-Oncogene Proteins c-kit / Q000172:deficiency / Q000235:genetics; D054390:Receptors, CCR2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D000804:Angiotensin II; D004549:Elastin; D019009:Proto-Oncogene Proteins c-kit