Protein I/II from oral viridans streptococci modulates expression of E-selectin, ICAM-1 and VCAM-1, and promotes transendothelial migration of neutrophils in vitro.

Abstract

Oral viridans streptococci which are major commensal bacteria of the oropharyngeal cavity have been associated with chronic as well as acute inflammatory diseases such as subacute endocarditis, subacute glomerulonephritis, rheumatic arthritis, sepsis and toxic shock. These diseases are probably the consequence of a local infection which has gain access to the bloodstream. Despite the fact that mechanisms of pathogenesis remained undefined, several reports have suggested that production in excess of proinflammatory cytokines may be involved in the development of the former diseases and we reported recently that oral viridans streptococci induce the release of TNF-α, IL-1β, IL-6, IL-8 from monocytes, of IL-6 and IL-8 from endothelial cells and of IL-6 from epithelial cells. We provide also evidence that oral viridans streptococci exert these effects probably by engaging two cell surface adhesins which belong to the recently defined class of modulins (1): protein I/II and a cell-wall polysaccharide (RGP). If RGP’s dependent signalling pathway appears to be related to binding to the CD14 receptor, protein I/II stimulates monocytes, epithelial and endothelial cells through lectin interactions. Accumulation of leucocytes in perivascular tissues is also a key step in inflammatory disorders and is correlated to a sequential upregulation of E-selectin, VCAM-1 and ICAM-1 expression on endothelium. Protein I/II, insofar as it is able to exert immunomodulatory effects on monocytes and endothelial cells, could contribute in an indirect or direct manner to the up-regulation, on endothelial cells of these adhesion molecules that allow binding and then penetration of leukocytes into tissues. This effect could contribute to the pathology of the diseases associated to oral viridans streptococci. To gain a broader insight into these mechanisms, we studied the direct effect of protein I/II on human saphenous vein endothelial cells (HSVEC) E-selectin, ICAM-1 and VCAM-1 expression and on the subsequent neutrophil migration.