The Journal of Immunology, Vol 158, Issue 11 5305-5313, Copyright © 1997 by American Association of Immunologists

ARTICLES

Listeria monocytogenes infection of cultured endothelial cells stimulates neutrophil adhesion and adhesion molecule expression

DA Drevets
Department of Medicine, R.C. Byrd Health Sciences Center of West Virginia University, Morgantown 26506, USA.

Microbial infection of the endothelium with the resultant up-regulation of adhesion molecule expression and stimulated leukocyte adhesion to endothelial cells can promote an inflammatory response. Previous work demonstrated that Listeria monocytogenes can replicate within cultured endothelial cells; thus, we tested whether L. monocytogenes infection of HUVEC stimulated an inflammatory phenotype on these cells. Infection with 10(4) CFU of bacteria increased neutrophil adhesion to HUVEC 40- fold and up-regulated E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 expression. Approximately 80% of neutrophil adhesion to infected HUVEC was blocked by anti-E-selectin mAb, 35% was blocked by anti-CD18 mAb, and anti-vascular cell adhesion molecule-1 mAb was without effect. Microscopy of infected HUVEC monolayers showed that neutrophils bound to infected and uninfected cells and that infected and uninfected HUVEC expressed E-selectin. Interestingly, uninfected HUVEC that bound neutrophils or expressed E- selectin typically were adjacent to infected cells. However, infected monolayers did not produce soluble factors that stimulated E-selectin expression on uninfected cells. Nuclear translocation of the p65 subunit of the transcription factor NF-kappaB accompanied the HUVEC response, and hemolysin secretion appeared critical for stimulating HUVEC. These studies show that L. monocytogenes infection stimulates up- regulation of adhesion molecule expression on endothelial cells, resulting in neutrophil adhesion to them. This response includes induction of an inflammatory phenotype on uninfected cells and may be triggered by listeriolysin O-mediated activation of host response mechanisms. Additionally, cell-to-cell spread of L. monocytogenes throughout the monolayer, without stimulating secondarily infected endothelial cells for neutrophil adhesion, is a possible means of immune avoidance.

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