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Published Online
on September 23, 2004

Arteriosclerosis, Thrombosis, and Vascular Biology. 2004
Published online before print September 23, 2004, doi: 10.1161/01.ATV.0000145979.82184.9f
A more recent version of this article appeared on November 1, 2004
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*Substance via MeSH

Submitted on March 8, 2004
Accepted on August 26, 2004

Severe Periodontitis Enhances Macrophage Activation via Increased Serum Lipopolysaccharide

Pirkko J. Pussinen *; Tiina Vilkuna-Rautiainen ; Georg Alfthan ; Timo Palosuo ; Matti Jauhiainen ; Jouko Sundvall ; Marja Vesanen ; Kimmo Mattila ; and Sirkka Asikainen

From the Institute of Dentistry (P.J.P., T.V.-R., M.V., K.M.), University of Helsinki, and the Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland; the Department of Health and Functional Ability (G.A., T.P., J.S.) and the Department of Molecular Medicine (M.J.), National Public Health Institute, Helsinki, Finland; and the Department of Oral Microbiology (S.A.), Umeå University, Umeå, Sweden.

* To whom correspondence should be addressed. E-mail: pirkko.pussinen{at}helsinki.fi.

Objective--In periodontitis, overgrowth of Gram-negative bacteria and access of lipopolysaccharide (LPS) to circulation may activate macrophages leading to foam cell formation. We investigated whether periodontal treatment affects proatherogenic properties of low-density lipoprotein (LDL) and, thus, macrophage activation.

Methods and Results--LDL was isolated and characterized before and after treatment from 30 systemically healthy patients with periodontitis. Production of cytokines and LDL cholesteryl ester (LDL-CE) uptake by macrophages (RAW 264.7) was determined. Baseline periodontal variables correlated positively with serum LPS and C-reactive protein concentrations, as well as macrophage cytokine production and LDL-CE uptake. LPS concentration correlated positively with serum concentration of oxidized LDL and cytokine production. Higher cytokine production and LDL-CE uptake were induced by LDL isolated from patients with elevated number of affected teeth before treatment. Patients with serum LPS concentrations above the median (0.87 ng/mL) at baseline had higher serum high-density lipoprotein (HDL) cholesterol (baseline versus after treatment, 1.30±0.19 versus 1.48±0.28 mmol/L; P=0.002) and HDL/LDL ratio (0.31±0.01 versus 0.34±0.10; P=0.048), but lower serum LPS concentration (1.70±0.49 versus 0.98±0.50 ng/mL; P=0.004) and autoantibodies to {beta}2-glycoprotein I (0.11±0.06 versus 0.09±0.04 EU; P=0.022) after treatment.

Conclusions--Our results suggest that in systemically healthy patients, the infected/inflamed area in periodontitis is associated with macrophage activation via increased serum LPS concentration.


Key words: inflammation • infection • lipoprotein metabolism • serum lipopolysaccharide




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