title: Impact of resolvin E1 on murine neutrophil phagocytosis in type 2 diabetes.
abstract: Diabetic complications involve inflammation-mediated microvascular and macrovascular damage, disruption of lipid metabolism, glycosylation of proteins, and abnormalities of neutrophil-mediated events. Resolution of inflamed tissues to health and homeostasis is an active process mediated by endogenous lipid agonists, including lipoxins and resolvins. This proresolution system appears to be compromised in type 2 diabetes (T2D). The goal of this study was to investigate unresolved inflammation in T2D. Wild-type (WT) and genetically engineered mice, including T2D mice (db/db), transgenic mice overexpressing the human resolvin E1 (RvE1) receptor (ERV1), and a newly bred strain of db/ERV1 mice, were used to determine the impact of RvE1 on the phagocytosis of Porphyromonas gingivalis in T2D. Neutrophils were isolated and incubated with fluorescein isothiocyanate-labeled P. gingivalis, and phagocytosis was measured in a fluorochrome-based assay by flow cytometry. Mitogen-activated protein kinase (MAPK) (p42 and p44) and Akt (Thr308 and Ser473) phosphorylation was analyzed by Western blotting. The mouse dorsal air pouch model was used to evaluate the in vivo impact of RvE1. Results revealed that RvE1 increased the neutrophil phagocytosis of P. gingivalis in WT animals but had no impact in db/db animals. In ERV1-transgenic and ERV1-transgenic diabetic mice, phagocytosis was significantly increased. RvE1 decreased Akt and MAPK phosphorylation in the transgenic animals. In vivo dorsal air pouch studies revealed that RvE1 decreases neutrophil influx into the pouch and increases neutrophil phagocytosis of P. gingivalis in the transgenic animals; cutaneous fat deposition was reduced, as was macrophage infiltration. The results suggest that RvE1 rescues impaired neutrophil phagocytosis in obese T2D mice overexpressing ERV1.
authors.affiliation: Department of Applied Oral Sciences, Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Bruno S
authors.initials: BS
authors.lastname: Herrera
authors.affiliation: Department of Applied Oral Sciences, Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Hatice
authors.initials: H
authors.lastname: Hasturk
authors.affiliation: Department of Applied Oral Sciences, Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Alpdogan
authors.initials: A
authors.lastname: Kantarci
authors.affiliation: Department of Applied Oral Sciences, Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Marcelo O
authors.initials: MO
authors.lastname: Freire
authors.affiliation: Department of Applied Oral Sciences, Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: Nguyen
authors.affiliation: Department of Applied Oral Sciences, Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Shevali
authors.initials: S
authors.lastname: Kansal
authors.affiliation: Department of Applied Oral Sciences, Forsyth Institute, Cambridge, Massachusetts, USA tvandyke@forsyth.org.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Van Dyke
mesh_terms: D000818:Animals; D016866:Bacteroidaceae Infections / Q000276:immunology; D001786:Blood Glucose; D048909:Diabetes Complications / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000276:immunology / Q000494:pharmacology; D005434:Flow Cytometry; D006031:Glycosylation; D007249:Inflammation / Q000276:immunology; D050356:Lipid Metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D009765:Obesity / Q000276:immunology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology*; D010766:Phosphorylation; D016966:Porphyromonas gingivalis / Q000276:immunology
chemical_list: D001786:Blood Glucose; D015118:Eicosapentaenoic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid