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. (July 2016)

• Record Type: Journal Article
• Authors: Rennert, Knut; Heisig, Kerstin; Groeger, Marko; Wallert, Maria; Funke, Harald; Lorkowski, Stefan; Huber, Otmar; Mosig, Alexander S.
• Is Part Of: Cytokine. Volume 83(2016)
• Page Start: 41
• Page End: 52
• Publication Date: 2016-07
• Subjects: 7AAD 7-aminoactinomycin -- ADAM17 a disintegrin and metallopeptidase domain 17 -- BB94 batimastat -- CBA cytometric bead array -- CCR2 chemokine (C-C motif) receptor 2 -- CD14 monocyte differentiation antigen CD14 -- CD16 Fcγ receptor III (FcγRIII) -- CX3CR1 CX3C chemokine receptor 1 -- FKN fractalkine, CX3CL1 -- HLA-DR major histocompatibility complex class II, DR -- HUVEC human umbilical vein endothelial cells -- ICAM-1 intercellular adhesion molecule 1 -- IL-1β interleukin-1β -- LPS lipopolysaccharide -- Ly6C lymphocyte antigen 6 complex, locus C1 -- MMP9 matrix metalloproteinase 9 -- NFκB nuclear factor κ-B -- sFKN soluble fractalkine -- TACE TNF-converting enzyme (ADAM17) -- TNF tumor necrosis factor -- VCAM-1 vascular cell adhesion protein 1 -- vWF von Willebrand factor; Monocytes -- Fractalkine -- LPS -- TNF -- CD16; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2016.03.017
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: CD16 + monocytes are efficiently recruited to endothelial cells (EC) in presence of LPS. TNF release is amplified upon CX3CR1-dependet CD16 + monocyte adhesion to EC. Fractalkine shed by CD16 + monocytes interferes with CD3CR1-dependent cell adhesion. Shedding of fractalkine thereby balances TNF release and CD16 + monocyte recruitment. 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.