The complement system is known to be a major effector mechanism of specific and nonspecific immunity against bacterial infections, and is thought to play a role in the pathogenesis of periodontal diseases. However, the interactions putatively pathogenic periodontal bacteria and the complement system have not been adequately studied. Recent studies indicate that several periodontal pathogens have the dual potential to both activate the complement system via the classical or alternative complement pathways and to generate proteolytic activities that could destroy individual complement proteins. It is also possible that fragments of complement proteins with biologic activity could result from bacterial mediated proteolysis of these proteins. For purposes of the proposed studies, a group of bacterial species including seven Bacteroides and two treponemes have been chosen for examination based upon their high incidence in plaque samples cultured from diseased periodontal sites and their observed ability to elicit proteolytic activity against various protein substrates in vitro.
The specific aims of the proposed research are to first examine the complement activation profiles of these selected species, and then to reexamine such profiles in the context of the organisms' abilities to release proteases that destroy individual purified complement proteins. The destruction of these proteins will be monitored by assessment of hemolytic activity and by electophoresis of radiolabelled proteins. In addition, when cleavage fragments are identified, they will be tested for appropriate biological activities. The long term objectives are to elucidate interactions between complement and periodontal pathogens that may afford protection to these organisms due to subversion of complement activation mechanisms, and which may influence inflammatory reactions in the periodontium.
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