Two Distinct Phospholipases C of Listeria monocytogenes Induce Ceramide Generation, Nuclear Factor-κB Activation, and E-Selectin Expression in Human Endothelial Cells

  • Schwarzer N
  • Nöst R
  • Seybold J
  • et al.
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Abstract

Infection of endothelial cells by Listeria monocytogenes is an essential step in the pathogenesis of listeriosis. We recently reported that L. monocytogenes induces up-regulation of E-selectin and other endothelial adhesion molecules and subsequent polymorphonuclear leukocyte (PMN) adhesion into cultured human endothelial cells. In the present study, we characterized the mechanisms of enhanced E-selectin expression using L. monocytogenes wild type (EGD), the isogenic in-frame deletion mutants for phosphatidylcholine (PC)- and phosphatidylinositol (PI)-specific phospholipases EGDΔplcA and EGDΔplcB, as well as the nonvirulent control strain Listeria innocua. Infection of endothelial cells with EGDΔplcA or EGDΔplcB for 6 h induced, as compared with EGD wild type, intermediate levels of E-selectin mRNA and protein as well as PMN rolling and adhesion at a shear rate of 1 dyne/cm2, indicating that both bacterial phospholipases are required for a maximal effect. Similarly, ceramide content and NF-κB activity were increased in L. monocytogenes-exposed endothelial cells, but only to intermediate levels for PC- or PI-phospholipase C (PLC)-deficient listerial mutants. Phospholipase effects could be mimicked by exogenously added ceramides or bacterial sphingomyelinase. The data presented indicate that PI-PLC and PC-PLC are important virulence factors for L. monocytogenes infections that induce accumulation of ceramides that in turn may act as second messengers to control host cell signal-transduction pathways leading to persistent NF-κB activation, increased E-selectin expression, and enhanced PMN rolling/adhesion. The ability of L. monocytogenes to stimulate PMN adhesion to endothelial cells may be an important mechanism in the pathogenesis of severe listeriosis.

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APA

Schwarzer, N., Nöst, R., Seybold, J., Parida, S. K., Fuhrmann, O., Krüll, M., … Suttorp, N. (1998). Two Distinct Phospholipases C of Listeria monocytogenes Induce Ceramide Generation, Nuclear Factor-κB Activation, and E-Selectin Expression in Human Endothelial Cells. The Journal of Immunology, 161(6), 3010–3018. https://doi.org/10.4049/jimmunol.161.6.3010

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