CYTOKINE PRODUCTION BY HUMAN EPITHELIAL AND ENDOTHELIAL-CELLS FOLLOWING EXPOSURE TO ORAL VIRIDANS STREPTOCOCCI INVOLVES LECTIN INTERACTIONSBETWEEN BACTERIA AND CELL-SURFACE RECEPTORS

In order to examine the possible implication of human epithelial and e ndothelial cells in the pathogenesis of various diseases associated wi th oral viridans streptococci, we tested the immunomodulatory effects of 11 representative strains of oral viridans streptococci on human ep ithelial KB cells and endothelial cells. We then examined the possible role of two major adhesins from oral viridans streptococci, protein I /II and rhammose-glucose polymers (RGPs), in this process. In this stu dy we demonstrate that oral viridans streptococci are potent stimulato rs of interleukin-8 (IL-8) production from KB cells and of IL-6 and IL -8 production from endothelial cells. The ability of protein I/II and RGPs to contribute to these effects was then examined. Using biotinyla ted protein I/IIf and RGPs from streptococcus mutans OMZ 175, we showe d that these adhesins bind to KB and endothelial cells through specifi c interactions and that the binding of these molecules initiates the r elease of IL-8 from KB cells and of IL-6 and IL-8 from endothelial cel ls. These results suggest that protein I/IIf and RGPs play an importan t role in the interactions between bacteria and KB and endothelial cel ls in that similar-cytokine profiles are obtained when cells are stimu lated with bacteria or surface components. We also provide evidence th at protein I/IIf binds to and stimulates KB and endothelial cells thro ugh lectin interactions and that N-acetyl neuraminic acid (NANA) and f ucose present on cell surface glycoproteins may form the recognition s ite since binding and cytokine release can be inhibited by dispase and periodate treatment of cells and by NANA and fucose. These results de monstrate that oral viridans streptococci, probably by engaging two ce ll surface adhesins, exert immunomodulatory effects on human KB and en dothelial cells.