title: 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.
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.
authors.affiliation: Center for Sepsis Control and Care, University Hospital Jena, Erlanger Allee 101, 07747 Jena, Germany; Institute of Biochemistry II, Jena University Hospital Jena, Nonnenplan 2-4, 07743 Jena, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Rennert
authors.affiliation: Work Group Molecular Hemostaseology, University Hospital Jena, Bachstrasse 18, 07743 Jena, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Heisig
authors.affiliation: Center for Sepsis Control and Care, University Hospital Jena, Erlanger Allee 101, 07747 Jena, Germany; Institute of Biochemistry II, Jena University Hospital Jena, Nonnenplan 2-4, 07743 Jena, Germany.
authors.forename: Marko
authors.initials: M
authors.lastname: Groeger
authors.affiliation: Department of Nutritional Biochemistry, Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Strasse 25, 07743 Jena, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Wallert
authors.affiliation: Work Group Molecular Hemostaseology, University Hospital Jena, Bachstrasse 18, 07743 Jena, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Funke
authors.affiliation: Department of Nutritional Biochemistry, Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Strasse 25, 07743 Jena, Germany; Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lorkowski
authors.affiliation: Center for Sepsis Control and Care, University Hospital Jena, Erlanger Allee 101, 07747 Jena, Germany; Institute of Biochemistry II, Jena University Hospital Jena, Nonnenplan 2-4, 07743 Jena, Germany.
authors.forename: Otmar
authors.initials: O
authors.lastname: Huber
authors.affiliation: Center for Sepsis Control and Care, University Hospital Jena, Erlanger Allee 101, 07747 Jena, Germany; Institute of Biochemistry II, Jena University Hospital Jena, Nonnenplan 2-4, 07743 Jena, Germany. Electronic address: alexander.mosig@med.uni-jena.de.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Mosig
mesh_terms: D000073883:CX3C Chemokine Receptor 1 / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D058851:GPI-Linked Proteins; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D008070:Lipopolysaccharides; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha
keywords: CD16; Fractalkine; LPS; Monocytes; TNF