Recruitment of CD16+ monocytes to endothelial cells in response to LPS-treatment and concomitant TNF release is regulated by CX3CR1 and interfered by soluble fractalkine |
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| Institution: | 1. Duke Clinical Research Institute, Durham, NC, USA;2. Academic Medical Center, University of Amsterdam, Department of Cardiology, Amsterdam, The Netherlands;3. Shaare Zedek Medical Centre, Jerusalem, Israel;4. Columbia University Medical Center and New York-Presbyterian Hospital and the Cardiovascular Research Foundation, NY, New York;5. Yale School of Medicine, New Haven, CT;6. Duke University Medical Center, Department of Cardiology, Durham, NC, USA;1. Department of Cardiology, Royal North Shore Hospital, Sydney, Australia;2. North Shore Heart Research Group, Kolling Institute of Medical Research, The University of Sydney, Sydney, Australia;1. Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstrasse 10, 07743 Jena, Germany;2. Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743 Jena, Germany;3. Center for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany;4. Institute of Biochemistry II, Jena University Hospital, Friedrich Schiller University Jena, Nonnenplan 2, 07743 Jena, Germany;5. Leibniz Institute for Age Research, Fritz Lipmann Institute Jena, Beutenbergstrasse 11, 07745 Jena, Germany |
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| Abstract: | Fractalkine (FKN, CX3CL1) is a regulator of leukocyte recruitment and adhesion, and controls leukocyte migration on endothelial cells (ECs). We show that FKN triggers different effects in CD16+ and CD16− monocytes, the two major subsets of human monocytes. In the presence of ECs a lipopolysaccharide (LPS)-stimulus led to a significant increase in tumor necrosis factor (TNF)-secretion by CD16+ monocytes, which depends on the interaction of CX3CR1 expressed on CD16+ monocytes with endothelial FKN. Soluble FKN that was efficiently shed from the surface of LPS-activated ECs in response to binding of CD16+ monocytes to ECs, diminished monocyte adhesion in down-regulating CX3CR1 expression on the surface of CD16+ monocytes resulting in decreased TNF-secretion. In this process the TNF-converting enzyme (TACE) acts as a central player regulating FKN-shedding and TNFα-release through CD16+ monocytes interacting with ECs. Thus, the release and local accumulation of sFKN represents a mechanism that limits the inflammatory potential of CD16+ monocytes by impairing their interaction with ECs during the initial phase of an immune response to LPS. This regulatory process represents a potential target for therapeutic approaches to modulate the inflammatory response to bacterial components. |
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| Keywords: | Monocytes Fractalkine LPS TNF CD16 |
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