Bartonella henselaeInduces NF-κB-Dependent Upregulation of Adhesion Molecules in Cultured Human Endothelial Cells: Possible Role of Outer Membrane Proteins as Pathogenic Factors

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Abstract
The endothelium is a specific target forBartonella henselae, and endothelial cell infection represents an important step in the pathogenesis of cat scratch disease and bacillary angiomatosis. Mechanisms ofBartonella-endothelial cell interaction as well as signaling pathways involved in target cell activation were analyzed.B. henselaestrain Berlin-1, isolated from bacillary angiomatosis lesions of a human immunodeficiency virus-infected patient, potently stimulated human umbilical cord vein endothelial cells (HUVEC), as determined by NF-κB activation and enhanced adhesion molecule expression. These effects were accompanied by increased PMN rolling on and adhesion to infected endothelial cell monolayers, as measured in a parallel-plate flow chamber assay. Monoclonal antibodies against E-selectin significantly reduced PMN rolling and adhesion. In our hands,B. henselaeBerlin-1 was substantially more active than the typing strainB. henselaeATCC 49882. E-selectin and ICAM-1 upregulation occurred for up to 9 days, as verified by Northern blotting and cell surface enzyme-linked immunosorbent assay. Induction of adhesion molecules was mediated via NF-κB activation and could be blocked by a specific NF-κB inhibitor. Additional studies indicated thatB. henselae-induced effects did not require living bacteria orBartonellalipopolysaccharides. Exposure of HUVEC to purifiedB. henselaeouter membrane proteins (OMPs), however, reproduced all aspects of endothelial cell activation. In conclusion,B. henselae, the causative agent of cat scratch disease and bacillary angiomatosis, infects and activates endothelial cells.B. henselaeOMPs are sufficient to induce NF-κB activation and adhesion molecule expression followed by enhanced rolling and adhesion of leukocytes. These observations identify important new properties ofB. henselae, demonstrating its capacity to initiate a cascade of events culminating in a proinflammatory phenotype of infected endothelial cells.