Abstract
In order to examine the possible implication of capsular polysaccharide (CP) types 5 and 8 (CP5 and CP8) from Staphylococcus aureus in the pathological mechanism associated with staphylococcal infections, we tested the immunomodulatory effects of CP5 and CP8 on human epithelial KB cells, endothelial cells, and monocytes. Using biotinylated CP5 and CP8, we provide evidence that both CPs bind to KB cells, endothelial cells, and monocytes in a dose- and calcium-dependent manner through specific interactions. These results were confirmed by competition experiments using soluble cell extracts. Furthermore, we show that CPs bind to identical cell membrane receptors on all three types of human cells and that human normal serum contains a factor(s) which inhibits the binding of both CPs to human KB cells, endothelial cells, and monocytes. The ability of CP5 and CP8 to stimulate the production of cytokines by the human cells was then examined. CP5 and CP8 trigger KB cells to produce interleukin-8 (IL-8); endothelial cells to produce IL-8 and IL-6; and monocytes to produce IL-8, IL-6, IL-1 beta, and tumor necrosis factor alpha. The release of cytokines by all three types of cells is time dependent and dose dependent, and the tumor necrosis factor alpha production by monocytes is not affected by the addition of polymyxin B. We further confirm that human normal serum inhibits the immunomodulatory effects of both polysaccharides on each kind of cell. These results confirm that S. aureus CPs act as bacterial adhesins having immunomodulatory effects for human cells.
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