Impaired phagocytosis in localized aggressive periodontitis: rescue by Resolvin E1

• Published in: PloS one Vol. 6; no. 9; p. e24422
• Main Authors: Fredman, Gabrielle, Oh, Sungwhan F, Ayilavarapu, Srinivas, Hasturk, Hatice, Serhan, Charles N, Van Dyke, Thomas E
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.09.2011; Public Library of Science (PLoS)
• Subjects: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid - metabolism; Abnormalities; Adult; Anesthesiology; B cells; Biology; Biosynthesis; Blood; Blood circulation; Blood platelets; Blood Platelets - drug effects; Blood Platelets - metabolism; Calcimycin; Calcimycin - pharmacology; Calcium Ionophores - pharmacology; Cardiovascular diseases; CD18 antigen; Cells, Cultured; Chromatography, Liquid; Disease; Drug dosages; Eicosapentaenoic acid; Eicosapentaenoic Acid - analogs & derivatives; Eicosapentaenoic Acid - pharmacology; Evacuations & rescues; Fatty acids; Female; Genes; Gum disease; Health care; Heart diseases; Hospitals; Humans; Hydroxyeicosatetraenoic Acids - metabolism; Inflammation; Inflammatory diseases; Integrins; Leukocytes (neutrophilic); Leukotriene B4 - metabolism; Lipoxin A4; Lipoxins - metabolism; Macrophages; Macrophages - cytology; Macrophages - drug effects; Male; Medicine; Middle Aged; Monocytes; Monocytes - drug effects; Monocytes - metabolism; Neutrophils; Neutrophils - drug effects; Neutrophils - metabolism; P-selectin; P-Selectin - metabolism; Pain; Periodontal disease; Periodontal diseases; Periodontitis; Periodontitis - metabolism; Phagocytes; Phagocytosis; Phagocytosis - drug effects; Physiological aspects; Platelets; Rodents; Tandem Mass Spectrometry; Type 2 diabetes; Womens health; United States > US; Massachusetts
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0024422

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.