Streptococcus suisstimulates ICAM-1 shedding from microvascular endothelial cells

Abstract

In this study, we hypothesized that Streptococcus suis induces the shedding of adhesion molecules from the surface of human brain microvascular endothelial cells (HBMEC), which may contribute to the ongoing pathophysiological processes of meningitis. When HBMEC were stimulated with whole cells of S. suis S735, significantly larger amounts of soluble intercellular adhesion molecule-1 (sICAM-1) were shed into conditioned medium while basal levels of soluble E-cadherin and P-selectin were unaffected. At a multiplicity of infection of 1 and 10, S. suis increased the concentration of sICAM-1 3.5- and 5-fold, respectively. A capsule-deficient mutant of S. suis induced more shedding than the parental strain. In addition, an S. suis cell wall preparation dose-dependently stimulated ICAM-1 shedding. Specific inhibitors of tyrosine kinase, mitogen-activated extracellular kinase 1, 2, and c-JUN N-terminal kinase significantly reduced S. suis-mediated ICAM-1 release. ICAM-1 shedding was also inhibited by a specific inhibitor of matrix metalloproteinases. The capacity of S. suis to induce ICAM-1 shedding has many functional implications that may contribute to the pathophysiological process of meningitis.

Intercellular adhesion molecule-1 is a regulator of blood–testis barrier function

“…7F). In the testis, proteolytic cleavage of membrane-bound ICAM-1 may be mediated by matrix metalloprotease-9 (MMP-9), similar to reports in other epithelia and endothelia (Grenier and Bodet, 2008), resulting in the release of sICAM-1 and in the timely disruption of BTB disassembly. This cleavage may be triggered by cytokines such as transforming growth factor-b (TGF-b), tumor necrosis factor a and interleukin-1a (IL-1a) or sICAM-1 may be working with cytokines to regulate BTB dynamics because cytokines have been shown to disrupt barrier function (Lie et al, 2011;Lui et al, 2001;Lui et al, 2003).…”

LasR-deficient Pseudomonas aeruginosa variants increase airway epithelial mICAM-1 expression and enhance neutrophilic lung inflammation

“…Although LPS expression or structures may vary across P. aeruginosa clinical strains, we doubt that this variable had a major effect on the ICAM-1 induction by the Early and Early ΔlasR strains since heat-inactivated filtrates of both strains, which contain heat-stable compounds such as LPS, stimulated mICAM-1 to comparable levels (Fig 2A). The P. aeruginosa type III effector ExoU also induces cleavage of mICAM-1 to soluble ICAM-1, but through a host cyclooxygenase-dependent pathway [77,78]. We note that the effect of P. aeruginosa ExoU on mICAM-1 does not explain our results since ExoU secretion requires an active type III secretion system [79] and is likely negligible in the cell-free P. aeruginosa filtrates used in our in vitro experimental system.…”

ICAM-1: Isoforms and Phenotypes

“…Expression of soluble ICAM-1 is, in part, cell-specific (endothelial and peripheral blood mononuclear cells) and modulated by cytokines such as IFN-1α (39). Soluble ICAM-1 is also generated by proteolytic cleavage of the membrane bound form by neutrophil elastase, cathepsin G, and bacteria-derived enzymes (42, 45, 46). Interestingly, the smaller ICAM-1 isoforms are more susceptible to proteolytic cleavage than the full-length isoform (42).…”