title: Critical role of the C5a-activated neutrophils in high-fat diet-induced vascular inflammation.
abstract: Exceed and chronic high-fat diet (HFD) contributes to the diagnosis and development of atherosclerosis, obesity, and metabolic syndrome. However, the key molecular component(s) triggered by HFD responsible for initiating vascular inflammation remain unknown. We observed that feeding HFD for 4 weeks is sufficient to induce leukocyte recruitment in the femoral artery of wild-type mice. Neutrophil- and monocyte-depletion analyses confirmed the preferential recruitment of neutrophils in these mice. Protein analysis of sera from HFD-fed mice revealed a marked elevation of complement component C5a levels. Exogenous C5a alone induced leukocyte recruitment, which was abolished by a C5a-receptor antagonist. We also examined the role of neutrophil-derived MCP-1 in accumulation of leukocytes in the artery. These results demonstrated a previously unrecognized role for C5a and neutrophils in the early onset of HFD-induced vascular inflammation. Further study may help in elucidating a novel regulatory pathway to control diet-induced inflammation such as that in case of atherosclerosis.
authors.affiliation: Department of Life Science and Bioethics, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.|Department of Nutrition and Metabolism in Cardiovascular Disease, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mizuko
authors.initials: M
authors.lastname: Osaka
authors.affiliation: Department of Life Science and Bioethics, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Honda
authors.affiliation: Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Inomata
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Egashira
authors.affiliation: Department of Life Science and Bioethics, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000276:immunology; D015936:Complement C5a / Q000276:immunology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D015870:Gene Expression; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D020556:Neutrophil Infiltration / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D017539:Tunica Intima / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014657:Vasculitis / Q000209:etiology* / Q000473:pathology
chemical_list: D018932:Chemokine CCL2; D015936:Complement C5a; D017493:Leukocyte Common Antigens