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

Vincents, Bjarne; Guentsch, Arndt; Kostolowska, Dominika; von Pawel-Rammingen, Ulrich; Eick, Sigrun; Potempa, Jan; Abrahamson, Magnus (2011). Cleavage of IgG1 and IgG3 by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis. FASEB journal, 25(10), pp. 3741-50. Bethesda, Md.: Federation of American Societies for Experimental Biology 10.1096/fj.11-187799

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > School of Dental Medicine > Department of Periodontology
UniBE Contributor:	Eick, Sigrun
ISSN:	0892-6638
Publisher:	Federation of American Societies for Experimental Biology
Language:	English
Submitter:	Eveline Carmen Schuler
Date Deposited:	04 Oct 2013 14:16
Last Modified:	05 Dec 2022 14:04
Publisher DOI:	10.1096/fj.11-187799
PubMed ID:	21768393
Web of Science ID:	000295356400042
URI:	https://boris.unibe.ch/id/eprint/4463 (FactScience: 208682)