Transvascular dissemination of Porphyromonas gingivalis from a sequestered site is dependent upon activation of the kallikrein/kinin pathway.
OBJECTIVE
Epidemiological evidence implicates a connection between human periodontitis and systemic diseases. One possible mechanism involves the direct dissemination of periodontopathogens to the target organs through the circulation. The aim of this work was to define the mechanism used by Porphyromonas gingivalis for dissemination from a sequestered infection site.


METHODS
BALB/c mice were subcutaneously infected with P. gingivalis via use of a mouse chamber model. Tissue fluids from various sites were collected and cultured to determine the presence of P. gingivalis. Evans Blue dye was used to measure the dissemination ability of P. gingivalis. Kinin-associated molecules were introduced into mice, and their effects on bacterial dissemination and mouse pathology were monitored.


RESULTS
P. gingivalis strain A7436 caused remote lesions and septicemia with severe cachexia, resulting in animal death. Intrachamber challenge with A7436 resulted in vascular permeability enhancement (VPE), as measured by the systemic infiltration of Evans Blue dye into chamber fluids. VPE was blocked by kininase and kinin receptor antagonist and enhanced by exogenous bradykinin and kininase inhibitor. Live bacteria were recovered from the subcutaneous perichamber and abdominal spaces (spreading), and from the blood (disseminating) of infected mice. Both kininase and kinin receptor antagonist reduced animal mortality as a result of infection with strain A7436 and decreased the number of bacteria recoverable from the blood, but they were not associated with bacterial spreading.


CONCLUSIONS
The results suggest that activation of the kinin system is involved in the breach of the vascular barrier that permits dissemination of P. gingivalis.
Hu
S-W
SW
Department of Dentistry, College of Oral Medicine, Chung Shan Medical University, Taichung, Taiwan.
Huang
C-H
CH
Huang
H-C
HC
Lai
Y-Y
YY
Lin
Y-Y
YY