An association between cardiovascular and periodontal disease may be due to lipopolysaccharide (LPS)-promoted release of inflammatory mediators, adverse alterations of the lipoprotein profile, and an imbalance in cholesterol homeostasis. Since periodontopathogenic potential differs between serotypes of a major periodontal pathogen, Actinobacillus actinomycetemcomitans, we studied the pro-atherogenic properties of LPS preparations from serotypes b and d strains on macrophages (RAW 264.7). A. actinomycetemcomitans LPS preparations induced a time-dependent release of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). LPS induced foam cell formation and cholesteryl ester accumulation from native low density lipoprotein in the following order: A. actinomycetemcomitans strains JP2 (serotype b) > Y4 (serotype b) > IDH781 (serotype d). mRNA expression levels of scavenger receptor class B, type-I, and ATP-binding cassette transporter-1, receptors mediating cholesterol efflux from macrophages, were decreased by LPS preparations. The results suggest that the pro-atherogenic potential of A. actinomycetemcomitans LPS may depend on the infecting strain and correlate with the periodontopathogenic potential of the pathogen.
Mattila KJ, Nieminen MS, Valtonen VV et al. Association between dental health and acute myocardial infarction . BMJ1989; 298: 779—781.
3.
Pussinen PJ, Vilkuna-Rautiainen T., Alfthan G. et al. Severe periodontitis enhances macrophage activation via increased serum lipopolysaccharide. Arterioscler Thromb Vasc Biol2004; 24: 2174—2180.
4.
Pussinen PJ, Jauhiainen M., Vilkuna-Rautiainen T. et al. Periodontitis decreases the antiatherogenic potency of high density lipoprotein. J Lipid Res2004; 45: 139—147.
5.
Holt SC, Bramanti TEFactors in virulence expression and their role in periodontal disease pathogenesis . Crit Rev Oral Biol Med1991; 2: 177—281.
6.
Pussinen PJ, Jousilahti P., Alfthan G., Palosuo T., Asikainen S., Salomaa V.Antibodies to periodontal pathogens are associated with coronary heart disease . Arterioscler Thromb Vasc Biol2003; 23: 1250—1254.
7.
Pussinen PJ, Nyyssönen K., Alfthan G., Salonen R., Laukkanen JA, Salonen JTSerum antibody levels to Actinobacillus actinomycetemcomitans predict the risk for coronary heart disease. Arterioscler Thromb Vasc Biol2005; 25: 833—838.
8.
Pussinen PJ, Alfthan G., Rissanen H., Reunanen A., Asikainen S., Knekt P.Antibodies to periodontal pathogens and stroke risk. Stroke2004; 35: 2020—2023.
9.
Haraszthy VI , Zambon JJ, Trevisan M., Zeid M., Genco RJIdentification of periodontal pathogens in atheromatous plaques. J Periodontol2000; 71: 1554—1560.
10.
Kozarov EV, Dorn BR, Shelburne CE, Dunn Jr WA, Progulske-Fox A.Human atherosclerotic plaque contains viable invasive Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. Arterioscler Thromb Vasc Biol2005; 25: E17—E18.
11.
Zambon JJ, Slots J., Genco RJSerology of oral Actinobacillus actinomycetemcomitans and serotype distribution in human periodontal disease. Infect Immun1983; 41: 19—27.
12.
Saarela M., Asikainen S., Jousimies-Somer H., Asikainen T., von Troil-Linden B., Alaluusua S.Hybridization patterns of Actinobacillus actinomycetemcomitans serotypes a—e detected with an rRNA gene probe. Oral Microbiol Immunol1993; 8: 111—115.
13.
Kaplan JB, Perry MB, MacLean LL, Furgang D., Wilson ME, Fine DHStructural and genetic analyses of O polysaccharide from Actinobacillus actinomycetemcomitans serotype f. Infect Immun2001; 69: 5375—5384.
14.
Page RC, Sims TJ, Engel LD et al. The immunodominant outer membrane antigen of Actinobacillus actinomycetemcomitans is located in the serotype-specific high-molecular-mass carbohydrate moiety of lipopolysaccharide. Infect Immun1991; 59: 3451—3462.
15.
Wilson ME, Schifferle REEvidence that the serotype b antigenic determinant of Actinobacillus actinomycetemcomitans Y4 resides in the polysaccharide moiety of lipopolysaccharide. Infect Immun1991; 59: 1544—1551.
Amano K., Nishihara T., Shibuya N., Noguchi T., Koga T.Immunochemical and structural characterization of a serotype-specific polysaccharide antigen from Actinobacillus actinomycetemcomitans Y4 (serotype b). Infect Immun1989; 57: 2942—2946.
18.
Califano JV , Schenkein HA, Tew JGImmunodominant antigen of Actinobacillus actinomycetemcomitans Y4 in high-responder patients. Infect Immun1989; 57: 1582—1589.
19.
Asikainen S. , Lai CH, Alaluusua S., Slots J.Distribution of Actinobacillus actinomycetemcomitans serotypes in periodontal health and disease. Oral Microbiol Immunol1991; 6: 115—118.
20.
Paju S., Carlson P., Jousimies-Somer H., Asikainen S.Heterogeneity of Actinobacillus actinomycetemcomitans strains in various human infections and relationships between serotype, genotype, and antimicrobial susceptibility. J Clin Microbiol2000; 38: 79—84.
21.
Pajukanta R. , Asikainen S., Saarela M., Alaluusua S., Jousimies-Somer H.In vitro antimicrobial susceptibility of different serotypes of Actinobacillus actinomycetemcomitans . Scand J Dent Res1993; 101: 299—303.
22.
Lakio L., Kuula H., Dogan B., Asikainen S.Actinobacillus actinomycetemcomitans proportion of subgingival bacterial flora in relation to its clonal type. Eur J Oral Sci2002; 110: 212—217.
23.
Dogan B., Saarela M., Asikainen S.Genotyping of Actinobacillus actinomycetemcomitans serotype d isolates based on polymerase chain reaction. Oral Microbiol Immunol1999; 14: 387—390.
24.
van Lenten BJ , Fogelman AMLipopolysaccharide-induced inhibition of scavenger receptor expression in human monocyte-macrophages is mediated through tumor necrosis factor-alpha. J Immunol1992; 148: 112—116.
25.
Funk JL, Feingold KR, Moser AH, Grunfeld C.Lipopolysaccharide stimulation of RAW 264.7 macrophages induces lipid accumulation and foam cell formation. Atherosclerosis1993 ; 98: 67—82.
26.
Baranova I. , Vishnyakova T., Bocharov A. et al. Lipopolysaccharide down regulates both scavenger receptor B1 and ATP binding cassette transporter A1 in RAW cells . Infect Immun2002; 70: 2995—3003.
27.
Agarwal S., Piesco NP, Johns LP, Riccelli AEDifferential expression of IL-1 beta, TNF-alpha, IL-6, and IL-8 in human monocytes in response to lipopolysaccharides from different microbes. J Dent Res1995; 74: 1057—1065.
28.
Barbour SE, Wong C., Rabah D., Kapur A., Carter ADMature macrophage cell lines exhibit variable responses to LPS. Mol Immunol1998; 35: 977—987.
29.
Stashenko P. , Fujiyoshi P., Obernesser MS, Prostak L., Haffajee AD, Socransky SSLevels of interleukin 1 beta in tissue from sites of active periodontal disease. J Clin Periodontol1991; 18: 548—554.
30.
Stashenko P. , Jandinski JJ, Fujiyoshi P., Rynar J., Socransky SSTissue levels of bone resorptive cytokines in periodontal disease. J Periodontol1991 ; 62: 504—509.
31.
Imatani T., Kato T., Okuda K.Production of inflammatory cytokines by human gingival fibroblasts stimulated by cell-surface preparations of Porphyromonas gingivalis. Oral Microbiol Immunol2001; 16: 65—72.
32.
Wiklund O., Carew TE, Steinberg D.Role of the low density lipoprotein receptor in penetration of low density lipoprotein into rabbit aortic wall. Arteriosclerosis1985; 5: 135—141.
33.
Van Lenten BJ , Fogelman AM, Haberland ME, Edwards PAThe role of lipoproteins and receptor-mediated endocytosis in the transport of bacterial lipopolysaccharide. Proc Natl Acad Sci USA1986; 83: 2704—2708.
34.
Kalayogly MV , Miranpuri GS, Golenbock DT, Byrne GICharacterization of low density lipoprotein uptake by murine macrophages exposed to Chlamydia pneumoniae. Microb Infect1999; 1: 409—418.
35.
Krieger M.Scavenger receptor class B type I is a multiligand HDL receptor that influences diverse physiologic systems. J Clin Invest2001; 108: 793—797.
36.
Lawn RM, Wade DP, Garvin MR et al. The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway. J Clin Invest1999; 104: R25—R31.
37.
Wang N., Lan D., Chen W., Matsuura F., Tall ARATP-binding cassette transporters G1 and G4 mediate cellular cholesterol efflux to high-density lipoproteins. Proc Natl Acad Sci USA2004; 101: 9774—9779.
38.
Khovidhunkit W., Moser AH, Shigenaga JK, Grunfeld C., Feingold KRRegulation of scavenger receptor class B type I in hamster liver and Hep3B cells by endotoxin and cytokines. J Lipid Res2001; 42: 1636—1644.
39.
Rietschel ET , Kirikae T., Schade FU et al. Bacterial endotoxin: molecular relationships of structure to activity and function. FASEB J1994; 8: 217—225.
40.
Kiley P., Holt SCCharacterization of the lipopolysaccharide from Actinobacillus actinomycetemcomitans Y4 and N27. Infect Immun1980; 30: 862—873.
41.
Brondz I., Olsen I.Differentiation between Actinobacillus actinomycetemcomitans and Haemophilus aphrophilus based on carbohydrates in lipopolysaccharide. J Chromatogr1984; 310: 261—272.
42.
Masoud H., Weintraub ST, Wang R., Cotter R., Holt SCInvestigation of the structure of lipid A from Actinobacillus actinomycetemcomitans strain Y4 and human clinical isolate PO 1021-7. Eur J Biochem1991; 200: 775—781.
43.
Perry MB, MacLean LM, Brisson JR, Wilson ME. Structures of the antigenic O-polysaccharides of lipopolysaccharides produced by Actinobacillus actinomycetemcomitans serotypes a, c, d and e. Eur J Biochem1996; 242: 682—688.
44.
Fine DH, Furgang D., Schreiner HC et al. Phenotypic variation in Actinobacillus actinomycetemcomitans during laboratory growth: implications for virulence. Microbiology1999; 145: 1335—1347.
45.
Geerts SO, Nys M., De MP et al. Systemic release of endotoxins induced by gentle mastication: association with periodontitis severity. J Periodontol2002; 73: 73—78.
46.
Saarela MH, Dogan B., Alaluusua S., Asikanen S.Persistence of oral colonization by the same Actinobacillus actinomycetemcomitans strain(s). J Periodontol1999; 70: 504—509.
