Infection of human endothelial cells with Staphylococcus aureus induces the production of monocyte chemotactic protein-1 (MCP-1) and monocyte chemotaxis

Bacterial infection coincides with migration of leucocytes from the circula tion into the bacterium-infected tissue. Recently, we have shown that endot helial cells, upon binding and ingestion of Staphylococcus aureus, exhibit proinflammatory properties including procoagulant activity and increased in tercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecul e-1 (VCAM-1) expression on the cell surface, resulting in hyperadhesiveness , mainly for monocytes. The enhanced extravasation of monocytes to bacteriu m-infected sites is facilitated by the local production of chemotactic fact ors. From another study we concluded that the locally produced chemokine MC P-1 is important in the recruitment of monocytes to the peritoneal cavity i n a model of bacterial peritonitis. In the present study we investigated wh ether cultured human endothelial cells after infection with bacteria produc e and release MCP-1, which in turn stimulates monocyte chemotaxis. We obser ved 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 vi rulence 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 c ells differed markedly from that released by endothelial cells upon stimula tion with IL-1 beta. Supernatant from S. aureus-infected or IL-1 beta-stimu lated cells promoted monocyte chemotaxis which was almost entirely abrogate d 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 super natant. Our findings support the notion that endothelial cells can actively initiate and sustain an inflammatory response after an encounter with path ogenic microorganisms, without the intervention of macrophage-derived proin flammatory cytokines.