title: Interleukin-10 and interferon-gamma modulate surface expression of fractalkine-receptor (CX(3)CR1) via PI3K in monocytes.
abstract: The membrane-anchored form of the chemokine fractalkine (CX(3)CL1) has been identified as a novel adhesion molecule that interacts with its specific receptor (CX(3)CR1) expressed in monocytes, T cells and natural killer cells to induce adhesion. In addition, CX(3)CL1 can be cleaved from the cell membrane to induce chemotaxis of CX(3)CR1-expressing leucocytes. Recently, marked variations in CX(3)CR1 monocyte expression have been observed during several pathological conditions. Regulation of CX(3)CR1 in monocytes during basal or inflammatory/anti-inflammatory conditions is poorly understood. The aim of this study was therefore to examine CX(3)CR1 expression during monocyte maturation and the effect of soluble mediators on this process. We found that basal expression of CX(3)CR1 in fresh monocytes was reduced during culture, and that lipopolysacchairde accelerated this effect. In contrast, interleukin-10 and interferon-gamma treatment abrogated CX(3)CR1 down-modulation, through a phosphatidylinositol 3 kinase-dependent pathway. Most importantly, CX(3)CR1 membrane expression correlated with monocyte CX(3)CL1-dependent function. Taken together, our data demonstrate that CX(3)CR1 expression in monocytes can be modulated, and suggest that alterations in their environment are able to influence CX(3)CL1-dependent functions, such as chemotaxis and adhesion, leading to changes in the kinetics, composition and/or functional status of the leucocyte infiltrate.
authors.affiliation: División Inmunología, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina.
authors.forename: María V
authors.initials: MV
authors.lastname: Ramos
authors.forename: Gabriela C
authors.initials: GC
authors.lastname: Fernández
authors.forename: Romina J Fernández
authors.initials: RJ
authors.lastname: Brando
authors.forename: Cecilia A
authors.initials: CA
authors.lastname: Panek
authors.forename: Leticia V
authors.initials: LV
authors.lastname: Bentancor
authors.forename: Verónica I
authors.initials: VI
authors.lastname: Landoni
authors.forename: Martín A
authors.initials: MA
authors.lastname: Isturiz
authors.forename: Marina S
authors.initials: MS
authors.lastname: Palermo
mesh_terms: D000073883:CX3C Chemokine Receptor 1; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000276:immunology; D013997:Time Factors
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D019707:Receptors, Chemokine; D016753:Interleukin-10; D007371:Interferon-gamma; D019869:Phosphatidylinositol 3-Kinases