title: Regulation of phagocytosis in macrophages by neuraminidase 1.
abstract: The differentiation of monocytes into macrophages and dendritic cells is accompanied by induction of cell-surface neuraminidase 1 (Neu1) and cathepsin A (CathA), the latter forming a complex with and activating Neu1. To clarify the biological importance of this phenomenon we have developed the gene-targeted mouse models of a CathA deficiency (CathA(S190A)) and a double CathA/Neu1 deficiency (CathA(S190A-Neo)). Macrophages of CathA(S190A-Neo) mice and their immature dendritic cells showed a significantly reduced capacity to engulf Gram-positive and Gram-negative bacteria and positively and negatively charged polymer beads as well as IgG-opsonized beads and erythrocytes. Properties of the cells derived from CathA(S190A) mice were indistinguishable from those of wild-type controls, suggesting that the absence of Neu1, which results in the increased sialylation of the cell surface proteins, probably affects multiple receptors for phagocytosis. Indeed, treatment of the cells with purified mouse Neu1 reduced surface sialylation and restored phagocytosis. Because Neu1-deficient cells showed reduced internalization of IgG-opsonized sheep erythrocytes whereas binding of the erythrocytes to the cells at 4 degrees C persisted, we speculate that the absence of Neu1 in particular affected transduction of signals from the Fc receptors for immunoglobulin G (FcgammaR). Indeed the macrophages from the Neu1-deficient mice showed increased sialylation and impaired phosphorylation of FcgammaR as well as markedly reduced phosphorylation of Syk kinase in response to treatment with IgG-opsonized beads. Altogether our data suggest that the cell surface Neu1 activates the phagocytosis in macrophages and dendritic cells through desialylation of surface receptors, thus, contributing to their functional integrity.
authors.affiliation: Sainte-Justine University Hospital Centre, University of Montreal, Montreal, QuebecH3T 1C5, Canada.
authors.forename: Volkan
authors.initials: V
authors.lastname: Seyrantepe
authors.forename: Alexandre
authors.initials: A
authors.lastname: Iannello
authors.forename: Feng
authors.initials: F
authors.lastname: Liang
authors.forename: Evgeny
authors.initials: E
authors.lastname: Kanshin
authors.forename: Preethi
authors.initials: P
authors.lastname: Jayanth
authors.forename: Suzanne
authors.initials: S
authors.lastname: Samarani
authors.forename: Myron R
authors.initials: MR
authors.lastname: Szewczuk
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmad
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Pshezhetsky
mesh_terms: D000818:Animals; D043402:Cathepsin A / Q000378:metabolism; D002454:Cell Differentiation; D002462:Cell Membrane / Q000201:enzymology; D003713:Dendritic Cells / Q000166:cytology; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000201:enzymology* / Q000382:microbiology; D051379:Mice; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000172:deficiency / Q000378:metabolism*; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis; D017452:Receptors, IgG / Q000276:immunology; D012756:Sheep; D015398:Signal Transduction; D013194:Staining and Labeling
chemical_list: D037102:Lectins; D009895:Opsonin Proteins; D017452:Receptors, IgG; C110128:Neu1 protein, mouse; D009439:Neuraminidase; D043402:Cathepsin A; D019158:N-Acetylneuraminic Acid