title: Activation of complement components C3 and C5 by a cysteine proteinase (gingipain-1) from Porphyromonas (Bacteroides) gingivalis.
abstract: Complement components C3 and C5 are susceptible to limited proteolysis by an arginine-specific cysteine proteinase isolated from Porphyromonas gingivalis. This bacterium is an anaerobe commonly associated with severe periodontal disease. Infection by P. gingivalis is accompanied by an acute inflammatory response, complete with extensive neutrophil involvement. This prompted us to investigate a possible direct role for complement in periodontitis evoked by P. gingivalis. Exposure of C3 and C5 to the cysteine proteinase at molar ratios between 1:25 and 1:100 (enzyme to substrate ratios) resulted in a time-dependent, limited degradation of each component. C3 was converted in a stepwise manner to C3a-like and C3b-like fragments with evidence of extensive further degradation of the C3a-like portion of the molecule. We were unable to demonstrate C3a activity in the C3 digestion mixtures. C3 degradation appears to involve primarily the alpha-chain. Proteolysis of C5 also progresses in a stepwise manner producing an initial internal cleavage of the alpha-chain to generate 30- and 86-kDa fragments. Further digestion of the 86-kDa amino-terminal fragment of the alpha-chain leads to the release of C5a or a C5a-like fragment that is biologically active for neutrophil activation. The fact that a potent chemotactic factor, i.e. C5a, can be generated from C5 by a proteinase derived from P. gingivalis suggests a recruiting mechanism for attracting neutrophils to the gingival lesion site in periodontal disease.
authors.affiliation: Department of Immunology, Institute of Scripps Clinic, La Jolla, California 92037.
authors.forename: J A
authors.initials: JA
authors.lastname: Wingrove
authors.forename: R G
authors.initials: RG
authors.lastname: DiScipio
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Potempa
authors.forename: J
authors.initials: J
authors.lastname: Travis
authors.forename: T E
authors.initials: TE
authors.lastname: Hugli
mesh_terms: D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D001439:Bacteroides / Q000201:enzymology*; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism*; D003182:Complement C5 / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D006801:Humans; D008969:Molecular Sequence Data
chemical_list: D018829:Adhesins, Bacterial; D003176:Complement C3; D003182:Complement C5; D000080867:Gingipain Cysteine Endopeptidases; D006388:Hemagglutinins; D003546:Cysteine Endopeptidases