title: Syk and Lyn phosphorylation induced by FcgammaRI and FgammaRII crosslinking is determined by the differentiation state of U-937 monocytic cells.
abstract: Fcgamma receptor (FcgammaR)-mediated phagocytosis by mononuclear phagocytes is an essential function in host defense. This process is initiated by crosslinking of membrane FcgammaRs, which induces phosphorylation and activation of Src and Syk tyrosine kinases. Activation of these enzymes is essential for initiating the biochemical cascade that results in the cytoskeletal and membrane changes involved in phagocytosis. Phagocytic capacity and other effector functions of mononuclear phagocytes change during differentiation/maturation of these cells. This is a complex process governed by different soluble and micro-environmental factors, giving rise to populations of cells with distinct phenotypic characteristics. Several agents, including calcitriol, have been shown to induce in vitro differentiation-related phenotypic changes in monocytic cell lines. In this paper, we characterized the changes in the initial biochemical signals associated with the increase in FcgammaR-mediated phagocytosis induced by calcitriol in monocytic U-937 cells. The 10-fold increase in phagocytic capacity is not accompanied by an increase in FcgammaR expression. However, the phosphorylation levels of Lyn and Syk after FcgammaRI or FcgammaRII crosslinking are increased after calcitriol treatment. Our results suggest that signaling induced by FcgammaR in mononuclear phagocytes is not only dependent on the quantity of FcgammaRs aggregated by a stimulus, but it is highly dependent on the cell's differentiation state.
authors: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México - UNAM, D.F.
authors: Claudia
authors: C
authors: Hallal-Calleros
authors: José
authors: J
authors: Agramonte-Hevia
authors: Claudia
authors: C
authors: Garay-Canales
authors: Janet M
authors: JM
authors: Oliver
authors: Cristhian
authors: C
authors: Guerra-Araiza
authors: David
authors: D
authors: Heras
authors: Ignacio
authors: I
authors: Camacho-Arroyo
authors: Isabel
authors: I
authors: Soto-Cruz
authors: Enrique
authors: E
authors: Ortega
mesh_terms: D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D018950:Lipopolysaccharide Receptors / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000378:metabolism*; D012313:RNA / Q000302:isolation & purification; D011951:Receptors, Complement / Q000187:drug effects / Q000378:metabolism; D017452:Receptors, IgG / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072377:Syk Kinase; D013997:Time Factors; D020298:U937 Cells; D019061:src-Family Kinases / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D004792:Enzyme Precursors; C489017:FCGR1A protein, human; D047908:Intracellular Signaling Peptides and Proteins; D018950:Lipopolysaccharide Receptors; D011951:Receptors, Complement; D017452:Receptors, IgG; D012313:RNA; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D002117:Calcitriol