Cleavage of IgG1 and IgG3 by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis
| Autor: | Sigrun Eick, Jan Potempa, Arndt Guentsch, Magnus Abrahamson, Bjarne Vincents, Ulrich von Pawel-Rammingen, Dominika Kostolowska |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Phagocytosis
medicine.medical_treatment Proteolysis Molecular Sequence Data Biochemistry cysteine peptidases Immunoglobulin G cysteine proteases Microbiology Research Communications 03 medical and health sciences immunoglobulin G 0302 clinical medicine enzyme kinetics Genetics medicine host-pathogen interactions Humans Amino Acid Sequence Adhesins Bacterial Periodontitis Molecular Biology Porphyromonas gingivalis Gingipain K 030304 developmental biology native substrates 0303 health sciences Protease biology medicine.diagnostic_test Fast protein liquid chromatography 030206 dentistry biology.organism_classification Cysteine Endopeptidases Host-Pathogen Interactions biology.protein Gingipain Cysteine Endopeptidases Antibody Biotechnology |
| Zdroj: | The FASEB Journal The FASEB Journal; Vol 25 |
| Popis: | 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 IgG1 was cleaved at a single site within the hinge region, generating Fab and Fc fragments. IgG3 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 IgG1 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 IgG1 and IgG3 by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis. |
| Databáze: | OpenAIRE |
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