Immunobiological Studies on the Pathogenic Mechanisms of Periodontal Disease

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Porphyromonas (Bacteroides) gingivalis, an anaerobic, black-pigmented rod, has been recognized as a major etiologic agent of periodontal disease. The organisms have peritrichous fimbriae ; the fimbriae were detached from fresh whole cells of P. gingivalis strain 381 by gentle pipetting and purified chromatographically using a DEAESepharose Fast Flow column. The purified fimbrial protein gave a single band of 41 KDa.Oral administration of P. gingivalis fimbriae with adjuvant GM-53 in liposomes, but not in Tris-HCI buffer, definitely enhanced the fimbria-specific serum IgG responses (IGGI>>IgG2b>IgG2a>IgG3) and IgA response in saliva of BALB/C mice. On the other hand, subcutaneous (s. c.) injection of fimbriae with GM-53 also raised the fimbria-specific IgG followed by IgA and IgM responses in serum, and both IgA and IgG responses in saliva. Oral immunization was less effective than s. c. injection in terms of the production of serum antibody in the mice. However, the level of salivary a … More ntibody of mice injected s. c. was similar to that of mice immunized orally. High anti-fimbriae IgG in serum were maintained in BALB/c mice immunized orally with fimbriae and GM-53 in liposomes for ca. 7 months after the primary immunizations. Oral administration also induced and held the fimbriaspecific IgA response in saliva for at least 6 months after the primary immunizations.We have shown that patients with adult periodontitis (AP) exhibited elevated serum IgG antibody levels to P. gingivalis fimbriae. The subclass response was IgG3>>IgGI>IgG2>>IgG4. Some IgA anti-fimbriae antibodies were also observed. IgAl predominated, but significant levels of IgA2 were also seen.We then assessed numbers of anti-fimbriae antibody-secreting cells from peripheral blood mononuclear cells (PBMC) and from inflamed gingiva of AP subjects by using a newly developed ELISPOT method. Gingival mononuclear cells (GMC) of AP subjects exhibited high numbers of spot-forming cells (SFC) including fimbriaespecific antibody secreting cells in a pattern of IgG>IgA>>IgM, while low numbers of SFC were seen in GMC from healthy gingiva. No fimbriae-specific SFC were seen in PBMC. It was also found GMC released increased levels of IL-5, IL-6 and TGF-beta but not IL-2 and IL4 when they were grown in vitro.Thus, we have examined pathogenic mechanisms of P. gingivalis in the development of periodontal disease from the veiw points of microbiology and immunology. Less