title: Infection of human endothelial cells with Staphylococcus aureus induces the production of monocyte chemotactic protein-1 (MCP-1) and monocyte chemotaxis.
abstract: Bacterial infection coincides with migration of leucocytes from the circulation into the bacterium-infected tissue. Recently, we have shown that endothelial cells, upon binding and ingestion of Staphylococcus aureus, exhibit proinflammatory properties including procoagulant activity and increased intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression on the cell surface, resulting in hyperadhesiveness, mainly for monocytes. The enhanced extravasation of monocytes to bacterium-infected sites is facilitated by the local production of chemotactic factors. From another study we concluded that the locally produced chemokine MCP-1 is important in the recruitment of monocytes to the peritoneal cavity in a model of bacterial peritonitis. In the present study we investigated whether cultured human endothelial cells after infection with bacteria produce and release MCP-1, which in turn stimulates monocyte chemotaxis. We observed that endothelial cells released significant amounts of MCP-1 within 48 h after ingestion of S. aureus. This was dependent on the number and the virulence of the bacteria used to infect the endothelial cells. The kinetics as well as the amount of MCP-1 released by S. aureus-infected endothelial cells differed markedly from that released by endothelial cells upon stimulation with IL-1beta. Supernatant from S. aureus-infected or IL-1beta-stimulated cells promoted monocyte chemotaxis which was almost entirely abrogated in the presence of neutralizing anti-MCP-1 antibody, indicating that most of the chemotactic activity was due to the release of MCP-1 into the supernatant. Our findings support the notion that endothelial cells can actively initiate and sustain an inflammatory response after an encounter with pathogenic microorganisms, without the intervention of macrophage-derived proinflammatory cytokines.
authors.affiliation: Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Tekstra
authors.forename: H
authors.initials: H
authors.lastname: Beekhuizen
authors.forename: J S
authors.initials: JS
authors.lastname: Van De Gevel
authors.forename: I J
authors.initials: IJ
authors.lastname: Van Benten
authors.forename: C W
authors.initials: CW
authors.lastname: Tuk
authors.forename: R H
authors.initials: RH
authors.lastname: Beelen
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte; D004730:Endothelium, Vascular / Q000166:cytology / Q000382:microbiology*; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology; D009000:Monocytes / Q000276:immunology / Q000382:microbiology / Q000502:physiology*; D013211:Staphylococcus aureus / Q000276:immunology / Q000502:physiology*
chemical_list: D018932:Chemokine CCL2; D007375:Interleukin-1