Oral Biosci Med 2 (2005), No. 4 27. Jan. 2006
Oral Biosci Med 2 (2005), No. 2-3 (30.08.2005)
Porphyromonas gingivalis LPS Lipid A Heterogeneity Significantly Affects Endothelial Cells Innate Host Responses
Darveau, Richard P./Reife, Robert A./Al-Qutub, Montaser/Bainbridge, Brian W./Coats, Stephen R./Braham, Pamela A.
Purpose: Porphyromonas gingivalis is an important gram-negative periopathogen strongly associated with adult type periodontitis. Lipopolysaccharide (LPS), a key component on the cell surface of gram-negative bacteria, is a potent immunomodulator that alerts the host of bacterial infection. The purpose of this study was to determine the contribution of P. gingivalis LPS heterogeneity to immunomodulation of innate host defenses.
Materials and Methods: P. gingivalis LPS was isolated and LPS heterogeneity was determined by a combination of matrix assisted laser desorption-time of flight (MALDI-TOF) mass spectroscopy coupled with gas chromatographic analysis of lipid A fatty acids. Endothelial cell E selectin activation was determined by semi-quantitative RT-PCR and IL-8 secretion was determined by ELISA.
Results: P. gingivalis lipid A heterogeneity was found to be due to culture medium conditions and extraction procedures and was not the result of degradation due to isolation procedures. Lipid A was identified as the component of LPS responsible for E selectin antagonism. Two different preparations of P. gingivalis LPS which differed in their lipid A species content were obtained. It was found that one was an agonist while the other was an antagonist for E selectin expression on human endothelial cells.
Conclusions: We suspect that the ability of P. gingivalis to synthesize and express multiple structurally different forms of lipid A represents a form of bacterially induced immunomodulation. This allows the bacterium to selectively evade and stimulate host cell responses in response to local environmental conditions contributing to its ability to occupy different niches in the host.
Keywords: lipopolysaccharide, innate defense, immunomodulation