Studies on periodontal pathogenic proteinases from Porphyromonas gingivalis and host cells

Abstract

Progressive periodontal disease is characterized by acute progressive lesions of gingival connective tissues, excessive leukocyte infiltration, and occurrence of a characteristic microflora. A variety of proteolytic enzymes derived from oral bacteria and host cells are found in gingival crevices and thought to play an important role in the onset and development of progressive periodontal disease. The anaerobic bacterium Porphyromonas gingivalis has been implicated in the etiology of the disease. Recently, we have purified a novel arginine-specific cysteine proteinase, termed "argingipain", from the culture supernatant of the organism. The enzyme was shown to have two important abilities related to the virulence of the organism. One is direct association with periodontal tissue breakdown through its abilities to degrade physiologically important proteins such as human collagens (type I and IV) and to evade inactivation by internal protease inhibitors. The other is associated with disruption of the normal host defense mechanisms through its abilities to degrade immunoglobulins and to inhibit the bactericidal activity of polymorphonuclear leukocytes. The virulence of argingipain was further substantiated by disruption of argingipain-encoding genes on the chromosome by use of suicide plasmid systems. On the other hand, we have studied roles of host cell-derived proteinases in the periodontal tissue breakdown. Levels of lysosomal proteinases such as cathepsins B, H, L, G and medullasin were determined in gingival crevicular fluid from periodontitis patients and experimental gingivitis subjects by activity measurement and sensitive immunoassay. The results suggested that all of these enzymes would be involved in the development of both gingivitis and periodontitis.