title: Staphylococcal peptidoglycan initiates an inflammatory response and procoagulant activity in human vascular endothelial cells: a comparison with highly purified lipoteichoic acid and TSST-1.
abstract: Staphylococcus aureus is one of the most significant pathogens in human sepsis and endocarditis. A hallmark of these endovascular S. aureus infections is that the coagulation system is triggered by a tissue factor (TF)-dependent pathway. This study demonstrates that highly purified S. aureus peptidoglycan, lipoteichoic acid (LTA) and TSST-1 increase TF mRNA and TF surface protein in human umbilical vein endothelial cells (ECs). Concomitantly, peptidoglycan- and LTA-activated ECs express significant TF-dependent procoagulant activity (TF PCA). In addition peptidoglycan, but not LTA or TSST-1, induced surface expression of the EC inflammation markers ICAM-1 and VCAM-1, which supported the adhesion of monocytes to these ECs. During the coculture of peptidoglycan-activated ECs and adherent monocytes, a marked additional increase of TF PCA was observed. Marginal increases in TF PCA were observed in cocultures of monocytes with LTA- or TSST-1-activated ECs. This study defines in particular staphylococcal peptidoglycan, previously known as a potent initiator of TF PCA in monocytes, as also being an activator of a coagulant response in human ECs that is further intensified by the presence of surface-bound monocytes.
authors.affiliation: Department of Microbiology, Eijkman-Winkler Institute, University Medical Center Utrecht, Utrecht, The Netherlands. e.mattsson@umcutrecht.nl
authors.forename: Eva
authors.initials: E
authors.lastname: Mattsson
authors.forename: Ruth
authors.initials: R
authors.lastname: Heying
authors.forename: Joke S
authors.initials: JS
authors.lastname: van de Gevel
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: Henry
authors.initials: H
authors.lastname: Beekhuizen
mesh_terms: D001427:Bacterial Toxins / Q000378:metabolism*; D001777:Blood Coagulation; D002448:Cell Adhesion; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000737:chemistry / Q000382:microbiology*; D004768:Enterotoxins / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology; D010457:Peptidoglycan / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013211:Staphylococcus aureus / Q000502:physiology*; D018089:Superantigens / Q000378:metabolism*; D013682:Teichoic Acids / Q000378:metabolism*; D013925:Thromboplastin / Q000096:biosynthesis* / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D012333:RNA, Messenger; D018089:Superantigens; D013682:Teichoic Acids; D019010:Vascular Cell Adhesion Molecule-1; C030107:enterotoxin F, Staphylococcal; D018799:Intercellular Adhesion Molecule-1; C009900:lipoteichoic acid; D013925:Thromboplastin