The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Cleavage of IgG1 and IgG3 by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis.

På svenska

Author

  • Bjarne Vincents
  • Arndt Guentsch
  • Dominika Kostolowska
  • Ulrich von Pawel-Rammingen
  • Sigrun Eick
  • Jan Potempa
  • Magnus Abrahamson

Summary, in English

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.-Vincents, B., Guentsch, A., Kostolowska, D., von Pawel-Rammingen, U., Eick, S., Potempa, J., Abrahamson, M. Cleavage of IgG(1) and IgG(3) by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis.

Publishing year

2011

Language

English

Pages

3741-3750

Publication/Series

FASEB Journal

Volume

25

Issue

10

Document type

Journal article

Publisher

Wiley

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Protease Inhibitor Research

ISBN/ISSN/Other

  • ISSN: 1530-6860