Vascular permeability enhancing activity of Porphyromonas gingivalis protease in guinea pigs

Abstract

Porphyromonas gingivalis protease, which had been isolated from a culture supernatant, caused vascular permeability enhancement in a dose-dependent manner when injected into guinea pig skin. The permeability-enhancing reaction caused by the protease was not affected by treatment with antihistamine, but was greatly augmented by simultaneous injection of a kinin potentiator, carboxypeptidase N inhibitor. However, the reaction was inhibited by soybean trypsin inhibitor or alpha 2-antiplasmin, although both of these inhibitors could not inhibit P. gingivalis protease at all by themselves. A bradykinin-degrading enzyme, carboxypeptidase B, weakened this vascular reaction. Results described indicate that the permeability-enhancing reaction induced by the protease is caused by activation, of the kallikrein-kinin cascade in the tissue.

Mechanisms MediatingPorphyromonas gingivalisGingipain RgpA-Induced Oral Mucosa Inflammation In Vivo

“…Moreover, a mixture of proteinase inhibitors, some of which have been shown to inhibit several steps in the kallikrein/kinin metabolic pathway but not gingipain RgpA activity (1, 12, 14-17, 20, 22), abrogated gingipain RgpA-induced responses. These data support and extend previous studies in the literature that showed that exogenous gingipains activate the kallikrein/kinin metabolic pathway in guinea pig skin and elicit plasma exudation (10,(14)(15)(16).…”

“…Leupeptin and a mixture of proteinase inhibitors also attenuated GRgpAinduced responses. These data indicate that GRgpA elicits plasma exudation from in situ oral mucosa in a catalytic site-dependent fashion by elaborating bradykinin.A large body of experimental evidence suggests that Porphyromonas gingivalis, an oral anaerobic bacterium, plays a role in the pathogenesis of adult periodontitis (2,9,(13)(14)(15)(16)32). A cardinal manifestation of this condition is plasma exudation from postcapillary venules (11,32).…”

“…However, the mechanisms underlying this response are uncertain (1,4,5,7,14,15,27). To this end, gingipain RgpA, a potent arginine-specific cysteine proteinase produced by P. gingivalis (2,12,16), has been shown to activate the kallikrein/kinin metabolic pathway in guinea pig skin to release bradykinin, a potent 9-amino-acid phlogistic mediator (1,7,33), thereby leading to plasma exudation (14,15). The purpose of this study was to determine whether gingipain RgpA elicits plasma exudation from in situ oral mucosa by elaborating bradykinin.…”

Gingipains: Critical Factors in the Development of Aspiration Pneumonia Caused by <b><i>Porphyromonas gingivalis</i></b>

“…One may, however, assume that hemorrhage was caused by the effect of gingipains on the respiratory epithelium, the endothelium lining capillary blood vessels, and components of the coagulation cascade. Degradation of tight-junction proteins by gingipains [74], together with enhanced vascular permeability [75], interference with blood clotting due to degradation of fibrinogen by Kgp [76], and protein C consumption by Rgps [77], most likely facilitate blood flow into lung tissues [78]. Also, the increased influx of neutrophils into the lung tissue of animals infected with W83 may exacerbate the local inflammatory response, thereby increasing tissue damage and, subsequently, bleeding and necrosis.…”

The Role of Gingipains in the Pathogenesis of Periodontal Disease

“…2). The ability of P. gingivalis proteinases to activate the kallikrein/kinin pathway was first described by Hinode et al 20 and Kaminishi et al 21 and later was studied in detail by Imamura et al 22,23 It was found that gingipains R are very potent vascular permeability enhancement (VPE) factors, inducing this activity through plasma prekallikrein activation and subsequent BK release. In this activity no significant difference was seen between HRgpA and RgpB.…”