Activation of ganglioside GM3 biosynthesis in human monocyte/macrophages during culturing in vitro

Gracheva, E. V.; Samovilova, N. N.; Golovanova, N. K.; Andreeva, E. R.; Андрианова, И. В.; Tararak, E.

doi:10.1134/s0006297907070127

Cited by 17 publications

(17 citation statements)

References 25 publications

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“…GM3 synthase catalyzes the transfer of a sialic acid residue to the terminal galactose of lactosylceramide, resulting in the synthesis of the ganglioside, GM3, the common precursor to nearly all of the cellular gangliosides (Kolter et al 2002). In agreement with early observations that GM3 levels increase upon macrophage-like cell differentiation (Nojiri et al 1986), the expression of GM3 synthase is dramatically upregulated upon monocyte differentiation into macrophages (Gracheva et al 2007). TNF-α and other proinflammatory mediators are also associated with increased GM3 synthase gene transcription and expression levels (Tagami et al 2002; Blander et al 1999).…”

Section: 2 Glycosphingolipidssupporting

confidence: 91%

Role of Glycosphingolipids in Dendritic Cell-Mediated HIV-1 Trans-infection

Puryear

Gummuluru

2012

Advances in Experimental Medicine and Biology

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Glycosphingolipids (GSLs) are components of the cell membrane that comprise a membrane bound lipid, ceramide, coupled to an extracellular carbohydrate. GSLs impact numerous aspects of membrane biology, including membrane fluidity, curvature, and organization. The role of these molecules in both chronic inflammation and infectious disease and underlying pathogenic mechanisms are just starting to be recognized. As a component of the cell membrane, GSLs are also incorporated into lipid bilayers of diverse enveloped viruses as they bud out from the host cell and can go on to have a significant influence on viral pathogenesis. Dendritic cell (DC) subsets located in the peripheral mucosal tissues are proposed to be one of the earliest cell types that encounter transmitted viruses and help initiate adaptive immune responses against the invading pathogen by interacting with T cells. In turn, viruses, as obligatory intracellular parasites, rely on host cells for completing their replication cycle, and not surprisingly, HIV has evolved to exploit DC biology for the initial transmission event as well as for its dissemination and propagation within the infected host. In this review, we describe the mechanisms by which GSLs impact DC-mediated HIV trans-infection by either modulating virus infectivity, serving as a direct virus particle-associated host-derived ligand for specific interactions with DCs, or modulating the T cell membrane in such a way as to impact viral entry and thereby productive infection of CD4+ T cells.

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Section: 2 Glycosphingolipidssupporting

confidence: 91%

Role of Glycosphingolipids in Dendritic Cell-Mediated HIV-1 Trans-infection

Puryear

Gummuluru

2012

Advances in Experimental Medicine and Biology

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“…Carbohydrate chains linked to glycoproteins and glycolipids are ligands to both bacterial and immune lectins such as selectins, galectins or 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 23 differentiation of human blood monocytes into macrophages 44 . Altogether, this strongly suggests that G M3 synthase may act as a metabolic bottleneck for the synthesis of the whole family of gangliosides, during monocyte-to-macrophage differentiation.…”

Section: Discussionmentioning

confidence: 99%

Glycosylation Changes Triggered by the Differentiation of Monocytic THP-1 Cell Line into Macrophages

et al. 2016

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The human acute monocytic leukemia cell line THP-1 is widely used as an in vitro phagocytic cell model because it exhibits several immune properties similar to native monocyte-derived macrophages. In this study, we investigated the alteration of N- and O-linked glycans as well as glycosphingolipids, during THP-1 differentiation, combining mass spectrometry, flow cytometry, and quantitative real-time PCR. Mass spectrometry revealed that macrophage differentiation led to a marked upregulation of expression of GM3 ganglioside as well as an increase in complex-type structures, particularly triantennary glycans, occurring at the expense of high-mannose N-glycans. Moreover, we observed a slight decrease in the proportion of multifucosylated N-glycans and α2,6-sialylation. The uncovered changes in glycosylation correlated with variations of gene expression of relevant glycosyltransferases and glycosidases including sialyltransferases, β-N-acetylglucosaminyltransferases, fucosyltransferases, and neuraminidase. Furthermore, using flow cytometry and antibodies directed against glycan structures, we confirmed that the alteration of glycosylation occurs at the cell surface of THP-1 macrophage-like cells. Altogether, we established that macrophagic maturation of THP-1 induces dramatic modifications of the surface glycosylation pattern that may result in differential interaction of monocytic and macrophagic THP-1 with immune or bacterial lectins.

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“…GM3 is known to be present in the plasma membrane of macrophages and activated CD4 + T cells (20,24), the primary targets of HIV-1 and therefore the primary cells from which de novo virions are produced in vivo. It has been well established that chronic immune activation is a hallmark of HIV-1 disease.…”

Section: Discussionmentioning

confidence: 99%

“…Although the previous assays demonstrated that modifications in the level of particle-associated GM3 or GM1 impacts the level of mDC capture, we sought to further verify this effect in a physiologically relevant cell type with naturally occurring differences in ganglioside levels. Whereas monocytes express a low level of membrane-associated GM3, this level is up-regulated either upon differentiation into macrophages (20) or upon immune activation (21). This dichotomy creates a tractable system wherein viruses are predicted to possess varying levels of GM3 when produced from differentially stimulated monocytes or macrophages.…”

Section: Liposome Model Of Virions Shows That the Inclusion Of α2-3-lmentioning

confidence: 99%

HIV-1 incorporation of host-cell–derived glycosphingolipid GM3 allows for capture by mature dendritic cells

Puryear

Ramirez

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

104

139

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The interaction between HIV and dendritic cells (DCs) is an important early event in HIV-1 pathogenesis that leads to efficient viral dissemination. Here we demonstrate a HIV gp120-independent DC capture mechanism that uses virion-incorporated hostderived gangliosides with terminal α2-3-linked sialic acid linkages. Using exogenously enriched virus and artificial liposome particles, we demonstrate that both α2-3 gangliosides GM1 and GM3 are capable of mediating this interaction when present in the particle at high levels. In the absence of overexpression, GM3 is the primary ligand responsible for this capture mechanism, because siRNA depletion of GM3 but not GM1 from the producer cell and hence virions, resulted in a dramatic decrease in DC capture. Furthermore, HIV-1 capture by DCs was competitively inhibited by targeting virion-associated GM3, but was unchanged by targeting GM1. Finally, virions were derived from monocytoid THP-1 cells that constitutively display low levels of GM1 and GM3, or from THP-1 cells induced to express high surface levels of GM1 and GM3 upon stimulation with the TLR2/1 ligand Pam3CSK4. Compared with untreated THP-1 cells, virus produced from Pam3CSK4-stimulated THP-1 cells incorporated higher levels of GM3, but not GM1, and showed enhanced DC capture and trans-infection. Our results identify a unique HIV-1 DC attachment mechanism that is dependent on a host-cell-derived ligand, GM3, and is a unique example of pathogen mimicry of host-cell recognition pathways that drive virus capture and dissemination in vivo.

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Activation of ganglioside GM3 biosynthesis in human monocyte/macrophages during culturing in vitro

Cited by 17 publications

References 25 publications

Role of Glycosphingolipids in Dendritic Cell-Mediated HIV-1 Trans-infection

Role of Glycosphingolipids in Dendritic Cell-Mediated HIV-1 Trans-infection

Glycosylation Changes Triggered by the Differentiation of Monocytic THP-1 Cell Line into Macrophages

HIV-1 incorporation of host-cell–derived glycosphingolipid GM3 allows for capture by mature dendritic cells

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