Listeria monocytogenes virulence factors that stimulate endothelial cells.
Listeria monocytogenes infection of endothelial cells upregulates surface expression of adhesion molecules and stimulates neutrophil adhesion to infected cell monolayers. The experiments presented here tested the roles of specific bacterial virulence factors as triggers for this inflammatory phenotype and function. Human umbilical vein endothelial cell (HUVEC) monolayers were infected with wild-type L. monocytogenes or L. monocytogenes mutants; then surface expression of E-selectin and neutrophil adhesion were measured. The results showed that delta hly and prfA mutants were the most crippled, requiring 100-fold more mutant bacteria than wild-type bacteria for analogous stimulation. By comparison, L. monocytogenes mutants with deletions of actA, inlA, inlB, inlAB, plcA, and plcB resembled their parent strains, and a delta plcA delta plcB mutant displayed decreased intracellular growth rate but only a minor decrease in stimulation of E-selectin or neutrophil adhesion. Other experiments showed that cytochalasin D-treated HUVEC monolayers bound bacteria, but internalization and increased surface E-selectin and intercellular adhesion molecule-1 expression were profoundly inhibited. However, cytochalasin D had no effect on the HUVEC response to stimulation with lipopolysaccharide or tumor necrosis factor alpha. These data suggest that listeriolysin O production by infecting L. monocytogenes contributes to increased expression of surface E-selectin and intercellular adhesion molecule-1, but neither it nor intracellular replication are directly responsible for this event. Nonetheless it is possible that listeriolysin O potentiates the effect(s) of an other molecule(s) that directly triggers this response. Additionally, cellular invasion by L. monocytogenes appears to be critical for initiating the HUVEC response, potentially by providing a signal which results in upregulation of the necessary bacterial genes.
Drevets
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DA
Department of Medicine, R. C. Byrd Health Sciences Center of West Virginia University, Morgantown 26506-9163, USA. ddrevets@wvu.edu
D001422:Bacterial Adhesion / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics; D001427:Bacterial Toxins; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D019040:E-Selectin / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D004727:Endothelium / Q000166:cytology / Q000382:microbiology; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006459:Hemolysin Factors / Q000235:genetics; D006460:Hemolysin Proteins; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics; D009504:Neutrophils / Q000378:metabolism; D010454:Peptide Termination Factors; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054799:Phospholipase C beta; D015398:Signal Transduction / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D010738:Type C Phospholipases / Q000235:genetics; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation; D014774:Virulence / Q000235:genetics
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D019040:E-Selectin; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D007074:Immunoglobulin G; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D010454:Peptide Termination Factors; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; C095768:inlB protein, Listeria monocytogenes; D018799:Intercellular Adhesion Molecule-1; C069761:internalin protein, Bacteria; C072980:actA protein, Listeria monocytogenes; D015638:Cytochalasin D; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D043265:Phosphatidylinositol Diacylglycerol-Lyase; C038705:hlyA protein, Listeria monocytogenes