INHIBITION OF C3 AND IGG PROTEOLYSIS ENHANCES PHAGOCYTOSIS OF PORPHYROMONAS-GINGIVALIS

In the face of an apparently competent immune response to Porphyromona s gingivalis, it is unclear how P. gingivalis evades the immune respon se and persists in human periodontitis. Particularly germane may be it s ability to resist phagocytosis by degrading and not binding serum op sonins. In our study, the resistance by invasive (W83 and A7436) and n oninvasive (ATCC 33277) P. gingivalis strains to phagocytosis by human neutrophils was compared with their C3- and IgG-proteolytic activity. The ability of opsonic human serum antibody to inhibit C3 proteolysis was also evaluated. Our results indicate that the more phagocytosis-r esistant invasive strains accumulate less I-125-C3 than the noninvasiv e strain; moreover, invasive strains degrade complement C3 in a dose-d ependent manner, inhibitable by rabbit antiserum or adult periodontiti s serum. Opsonization and C3 accumulation on strain A7436 were both fa cilitated by pretreatment with rabbit antiserum, certain adult periodo ntitis sera, protease inhibitors (p-chloromercuriphenylsulfonic acid, Nalpha-p-tosyl-L-lysine chloromethyl ketone, diisopropylfluorophosphat e), heat (60-degrees-C, 15 min), and were Mg2+ dependent. The sera fro m 13 human subjects with or without periodontitis were assayed for ant ibody titers to P. gingivalis (ELISA units), opsonic activity (% of PM N engaged in phagocytosis) and enhancement of C3 accumulation. Statist ically significant associations were observed between % of PMN engaged in phagocytosis and % C3 accumulation, between % of PMN engaged in ph agocytosis and ELISA units and between % C3 accumulation and ELISA uni ts. Degradation of purified rabbit IgG, but not specific antibody-cont aining rabbit IgG by P. gingivalis A7436 was observed, and was inhibit ed by diisopropyl fluorophosphate (DFP) or cold (2-degrees-C). Our dat a suggest that C3 and IgG cleavage by P. gingivalis proteases are inhi bitable by antibody and are contributory factors in, but are not the s ole determinants of, phagocytosis resistance.