title: Cleavage of IgG1 and IgG3 by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis.
abstract: Degradation of immunoglobulins is an effective strategy of bacteria to evade the immune system. We have tested whether human IgG is a substrate for gingipain K of Porphyromonas gingivalis and found that the enzyme can hydrolyze subclass 1 and 3 of human IgG. The heavy chain of IgG(1) was cleaved at a single site within the hinge region, generating Fab and Fc fragments. IgG(3) was also cleaved within the heavy chain, but at several sites around the CH2 region. Investigation of the enzyme kinetics of IgG proteolysis by gingipain K, using FPLC- and isothermal titration calorimetry-based assays followed by Hill plots, revealed non-Michaelis-Menten kinetics involving a mechanism of positive cooperativity. In ex vivo studies, it was shown that gingipain K retained its IgG hydrolyzing activity in human plasma despite the high content of natural protease inhibitors; that IgG(1) cleavage products were detected in gingival crevicular fluid samples from patients with severe periodontitis; and that gingipain K treatment of serum samples from patients with high antibody titers against P. gingivalis significantly hindered opsonin-dependent phagocytosis of clinical isolates of P. gingivalis by neutrophils. Altogether, these findings underline a biological function of gingipain K as an IgG protease of pathophysiological importance.
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Chemistry and Pharmacology, Lund University, University Hospital, SE-221 85 Lund, Sweden.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Vincents
authors.forename: Arndt
authors.initials: A
authors.lastname: Guentsch
authors.forename: Dominika
authors.initials: D
authors.lastname: Kostolowska
authors.forename: Ulrich
authors.initials: U
authors.lastname: von Pawel-Rammingen
authors.forename: Sigrun
authors.initials: S
authors.lastname: Eick
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
authors.forename: Magnus
authors.initials: M
authors.lastname: Abrahamson
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism / Q000494:pharmacology*; D000595:Amino Acid Sequence; D003546:Cysteine Endopeptidases / Q000378:metabolism / Q000494:pharmacology*; D000080867:Gingipain Cysteine Endopeptidases; D054884:Host-Pathogen Interactions; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D008969:Molecular Sequence Data; D010518:Periodontitis / Q000382:microbiology / Q000473:pathology*; D016966:Porphyromonas gingivalis / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D000080867:Gingipain Cysteine Endopeptidases; D007074:Immunoglobulin G; D003546:Cysteine Endopeptidases