title: Impaired phagocytosis in localized aggressive periodontitis: rescue by Resolvin E1.
abstract: Resolution of inflammation is an active temporally orchestrated process demonstrated by the biosynthesis of novel proresolving mediators. Dysregulation of resolution pathways may underlie prevalent human inflammatory diseases such as cardiovascular diseases and periodontitis. Localized Aggressive Periodontitis (LAP) is an early onset, rapidly progressing form of inflammatory periodontal disease. Here, we report increased surface P-selectin on circulating LAP platelets, and elevated integrin (CD18) surface expression on neutrophils and monocytes compared to healthy, asymptomatic controls. Significantly more platelet-neutrophil and platelet-monocyte aggregates were identified in circulating whole blood of LAP patients compared with asymptomatic controls. LAP whole blood generates increased pro-inflammatory LTB4 with addition of divalent cation ionophore A23187 (5 µM) and significantly less, 15-HETE, 12-HETE, 14-HDHA, and lipoxin A(4). Macrophages from LAP subjects exhibit reduced phagocytosis. The pro-resolving lipid mediator, Resolvin E1 (0.1-100 nM), rescues the impaired phagocytic activity in LAP macrophages. These abnormalities suggest compromised resolution pathways, which may contribute to persistent inflammation resulting in establishment of a chronic inflammatory lesion and periodontal disease progression.
authors.affiliation: Department of Periodontology, The Forsyth Institute, Cambridge, Massachusetts, United States of America.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Fredman
authors.forename: Sungwhan F
authors.initials: SF
authors.lastname: Oh
authors.forename: Srinivas
authors.initials: S
authors.lastname: Ayilavarapu
authors.forename: Hatice
authors.initials: H
authors.lastname: Hasturk
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Van Dyke
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D061207:Calcium Ionophores / Q000494:pharmacology; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D044045:Lipoxins / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D010518:Periodontitis / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D053719:Tandem Mass Spectrometry
chemical_list: D061207:Calcium Ionophores; D006893:Hydroxyeicosatetraenoic Acids; D044045:Lipoxins; D019007:P-Selectin; D007975:Leukotriene B4; D000001:Calcimycin; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D015118:Eicosapentaenoic Acid; C499823:5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid