Degradation of complement regulatory protein CD46 by Porphyromonas gingivalis

Objectives: The complement system plays an important role in the host defense against pathogenic microorganisms. However, if not properly regulated, activated complement can also cause significant damage to host tissues. To prevent complement-mediated autologous tissue damage, host cells express a number of membrane-bound complement regulatory proteins. The aim of this study was to investigate the effect of Porphyromonas gingivalis, the major etiologic agent of chronic periodontitis, on the complement regulatory protein CD46 expressed on oral epithelial cells. Methods: The susceptibility of recombinant human CD46 to P. gingivalis cells and to purified Arg- and Lys-gingipains was evaluated by SDS-PAGE/Western immunoblotting analysis. The shedding/proteolysis of CD46 expressed on the surface of oral epithelial cells was also investigated. Results: P. gingivalis cells as well as Arg- and Lys-gingipains degrade CD46 in a dose- and time-dependent manner. P. gingivalis gingipains also induce the shedding/proteolysis of membrane-anchored CD46 expressed by oral epithelial cells. Conclusion: This study shows the ability of P. gingivalis to degrade CD46. This may render host cells susceptible to the complement system and contribute to tissue damage. This study was supported by the Canadian Institutes of Health Research.