Phosphorylcholine-dependent cross-reactivity between dental plaque bacteria and oxidized low-density lipoproteins.
Antibodies reactive with phosphorylcholine (PC) are ubiquitous in human sera, but the antigens stimulating their production and their function are not clear. Previous studies have shown that a significant proportion of dental plaque bacteria contain PC as determined by reactivity with PC-specific mouse myeloma proteins and monoclonal antibodies. Additionally, serum antibody concentrations of immunoglobulin (IgG) G anti-PC are higher in sera of individuals who have experienced periodontal attachment loss than those who are periodontally healthy. These data implicate the oral microflora as a source of antigen-stimulating anti-PC responses. Recent data also indicate that antibodies with specificity for PC are elevated in ApoE-deficient mice, a model for studies of athersclerosis, and that such antibodies bound oxidized low-density lipoproteins (LDL) (oxLDL) in atherosclerotic plaques. These data prompted the hypothesis that human anti-PC could bind to both oral bacteria and human oxLDL, and that these antigens are cross-reactive. We therefore examined the ability of human anti-PC to bind to PC-bearing strains of oral bacteria using enzyme-linked immunosorbent inhibition assays and by assessment of direct binding of affinity-purified human anti-PC to PC-bearing Actinobacillus actinomycetemcomitans. Our results indicated that PC-bearing strains of Streptococcus oralis, Streptococcus sanguis, Haemophilus aphrophilus, Actinomyces naeslundii, Fusobacterium nucleatum, and A. actinomycetemcomitans, as well as a strain of Streptococcus pneumoniae, absorbed up to 80% of anti-PC IgG antibody from human sera. Furthermore, purified anti-PC bound to a PC-bearing strain of A. actinomycetemcomitans but only poorly to a PC-negative strain. OxLDL also absorbed anti-PC from human sera, and oxLDL but not LDL reacted with up to 80% of the anti-PC in human sera. Furthermore, purified anti-PC bound directly to oxLDL but not to LDL. The data indicate that PC-containing antigens on a variety of common oral bacteria are cross-reactive with neoantigens expressed in oxLDL. We propose that PC-bearing dental plaque microorganisms may induce an antibody response to PC that could influence the inflammatory response associated with atherosclerosis.
Schenkein
H A
HA
Clinical Research Center for Periodontal Disease, School of Dentistry, Virginia Commonwealth University, Richmond, Virginia 23298, USA. hschenke@hsc.vcu.edu
Berry
C R
CR
Purkall
D
D
Burmeister
J A
JA
Brooks
C N
CN
Tew
J G
JG
D000190:Actinomyces / Q000276:immunology; D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology; D000907:Antibodies, Bacterial / Q000276:immunology; D001419:Bacteria / Q000276:immunology; D003429:Cross Reactions; D003773:Dental Plaque / Q000382:microbiology*; D016967:Fusobacterium nucleatum / Q000276:immunology; D006190:Haemophilus / Q000276:immunology; D006801:Humans; D008077:Lipoproteins, LDL / Q000276:immunology*; D010767:Phosphorylcholine / Q000276:immunology*; D019533:Streptococcus oralis / Q000276:immunology; D013298:Streptococcus sanguis / Q000276:immunology
D000907:Antibodies, Bacterial; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D010767:Phosphorylcholine