Listeria monocytogenes potently induces up-regulation of endothelial adhesion molecules and neutrophil adhesion to cultured human endothelial cells.
Infection of endothelial cells by Listeria monocytogenes is an essential step in the pathogenesis of listeriosis. Listeriolysin (Hly) is one of its major virulence factors. In the early phase of the disease polymorphonuclear leukocytes (PMN) substantially contribute to the nonspecific anti-listerial resistance. We characterized the effects of L. monocytogenes on the expression of endothelial adhesion molecules and on subsequent PMN adhesion to cultured HUVEC. P-selectin, E-selectin, intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) were up-regulated in HUVEC after cell incubation with L. monocytogenes (wild type), but not with the nonpathogenic Listeria innocua strain. P-selectin expression peaked after 30 min and could be mimicked with similar kinetics by exposure to L. innocua engineered to produce large amounts of Hly or by addition of purified Hly. Listeriolysin production, however, was not necessary for an up-regulation of E-selectin after 6 h or of ICAM-1 and VCAM-1 after 18 to 24 h in HUVEC, because L. monocytogenes defective for Hly synthesis was almost as effective as the wild type. Listeria-induced up-regulation of endothelial adhesion molecules was accompanied by an increased binding of PMN to infected HUVEC. PMN adhesion was significantly reduced in the presence of anti-beta2 integrin, anti-E-selectin, and anti-ICAM-1, but not anti-VCAM-1 Abs. Our data indicate that infection of endothelial cells with L. monocytogenes induced up-regulation of adhesion molecules by two different mechanisms: a Hly-dependent up-regulation of P-selectin and a Hly-independent expression of E-selectin, ICAM-1, and VCAM-1. The ability of L. monocytogenes to stimulate PMN adhesion to endothelial cells may be an important mechanism in the pathogenesis of severe listeriosis.
Krüll
M
M
Department of Internal Medicine, Justus Liebig University, Giessen, Germany.
Nöst
R
R
Hippenstiel
S
S
Domann
E
E
Chakraborty
T
T
Suttorp
N
N
D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1