Lipoteichoic acid inhibits lipopolysaccharide-induced adhesion molecule expression and IL-8 release in human lung microvascular endothelial cells.
Cell adhesion molecule expression (CAM) and IL-8 release in lung microvascular endothelium facilitate neutrophil accumulation in the lung. This study investigated the effects of lipoteichoic acid (LTA), a cell wall component of Gram-positive bacteria, alone and with LPS or TNF-alpha, on CAM expression and IL-8 release in human lung microvascular endothelial cells (HLMVEC). The concentration-dependent effects of Staphylococcus aureus (S. aureus) LTA (0.3-30 microg/ml) on ICAM-1 and E-selectin expression and IL-8 release were bell shaped. Streptococcus pyogenes (S. pyogenes) LTA had no effect on CAM expression, but caused a concentration-dependent increase in IL-8 release. S. aureus and S. pyogenes LTA (30 microg/ml) abolished LPS-induced CAM expression, and S. aureus LTA reduced LPS-induced IL-8 release. In contrast, the effects of S. aureus LTA with TNF-alpha on CAM expression and IL-8 release were additive. Inhibitory effects of LTA were not due to decreased HLMVEC viability, as assessed by ethidium homodimer-1 uptake. Changes in neutrophil adhesion to HLMVEC paralleled changes in CAM expression. Using RT-PCR to assess mRNA levels, S. aureus LTA (3 microg/ml) caused a protein synthesis-dependent reduction (75%) in LPS-induced IL-8 mRNA and decreased the IL-8 mRNA half-life from >6 h with LPS to approximately 2 h. These results suggest that mechanisms exist to prevent excessive endothelial cell activation in the presence of high concentrations of bacterial products. However, inhibition of HLMVEC CAM expression and IL-8 release ultimately may contribute to decreased neutrophil accumulation, persistence of bacteria in the lung, and increased severity of infection.
Blease
K
K
Applied Pharmacology and Unit of Critical Care, National Heart and Lung Institute Division, Imperial College School of Medicine, London, United Kingdom.
Chen
Y
Y
Hellewell
P G
PG
Burke-Gaffney
A
A
D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D004347:Drug Interactions; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects*; D006207:Half-Life; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply*; D008171:Lung Diseases / Q000276:immunology; D008833:Microcirculation; D020556:Neutrophil Infiltration; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D018805:Sepsis / Q000276:immunology; D013291:Streptococcus / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology; D013682:Teichoic Acids / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; C009900:lipoteichoic acid