Biphasic Effect of Gingipains from Porphyromonas gingivalis on the Human Complement System.
Författare
Summary, in English
Periodontitis is an inflammatory disease of the supporting structures of the teeth and is caused by, among other agents, Porphyromonas gingivalis. P. gingivalis is very resistant to killing by human complement, which is present in a gingival fluid at 70% of the serum concentration. We found that the incubation of human serum with purified cysteine proteases of P. gingivalis (gingipains) or P. gingivalis wild-type strains W83 and W50 resulted in a drastic decrease of the bactericidal activity of the serum. In contrast, serum treated with P. gingivalis mutants lacking gingipains (particularly strains without HRgpA) maintained significant bactericidal activity. To understand in detail the mechanism by which gingipains destroy the serum bactericidal activity, we investigated the effects of gingipains on the human complement system. We found that all three proteases degraded multiple complement components, with arginine-specific gingipains (HRgpA and RgpB) being more efficient than lysine-specific gingipain (Kgp). Interestingly, all three proteases at certain concentrations were able to activate the CI complex in serum, which resulted in the deposition of C1q on inert surfaces and on bacteria themselves. It is therefore plausible that P. gingivalis activates complement when present at low numbers, resulting in a local inflammatory reaction and providing the bacteria with a colonization opportunity and nutrients. At later stages of infection the concentration of proteases is high enough to destroy complement factors and thus render the bacteria resistant to the bactericidal activity of complement.
Publiceringsår
2007
Språk
Engelska
Sidor
7242-7250
Publikation/Tidskrift/Serie
Journal of Immunology
Volym
178
Issue
11
Dokumenttyp
Artikel i tidskrift
Förlag
American Association of Immunologists
Ämne
- Immunology in the medical area
Status
Published
Forskningsgrupp
- Clinical Chemistry, Malmö
- Protein Chemistry, Malmö
- Clinical Microbiology, Malmö
ISBN/ISSN/Övrigt
- ISSN: 1550-6606