Lysophosphatidylcholine-mediated functional inactivation of syndecan-4 results in decreased adhesion and motility of dendritic cells.

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Lysophosphatidylcholine-mediated functional inactivation of syndecan-4 results in decreased adhesion and motility of dendritic cells. / Bühligen, Johannes; Himmel, Mirko; Gebhardt, Carl; Simon, Jan C; Ziegler, Wolfgang; Averbeck, Marco.

in: J CELL PHYSIOL, Jahrgang 225, Nr. 3, 3, 2010, S. 905-914.

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@article{6a183aa93c694773906c2e5c0cdc9de7,
title = "Lysophosphatidylcholine-mediated functional inactivation of syndecan-4 results in decreased adhesion and motility of dendritic cells.",
abstract = "Following antigen contact, maturation and migration of DCs into lymphatic tissues are crucial to the developing immune response or maintenance of tolerance. Lysophosphatidylcholine (LysoPC) is generated during apoptosis of cells and acts as a {"}find-and-eat-me{"} signal thought to prevent autoimmunity. Moreover, LysoPC can activate PKC and initiates a signaling cascade that leads to phosphorylation and inactivation of syndecan-4 (SDC4), a heparansulfate proteoglycan integrin co-receptor. In human monocyte-derived DCs, we recently demonstrated that SDC4 is upregulated during maturation thereby stimulating DC motility. Here, we investigate the effects of LysoPC on DC motility as well as on the involvement of PKC phosphorylation-dependent regulation of DC motility by SDC4 and PKC . Employing a static adhesion assay and videomicroscopy, we show that LysoPC inhibits adhesion of DCs to fibronectin and motility of DCs by decreasing podosome formation. Moreover, DC podosome formation and motility, which both are regulated by SDC4 and subject to control by PKC -dependent phosphorylation of SDC4, were inhibited in LysoPC-matured DCs. Thus, these DC are defective in adhesion and migration. Based on our results, we hypothesize that LysoPC released during apoptosis might delay DC migration to lymphoid organs and thus prevent autoimmunity.",
keywords = "Humans, Cells, Cultured, Cell Movement, Membrane Proteins metabolism, Apoptosis, Dendritic Cells immunology, Phosphorylation, Antigens, CD86 metabolism, Autoimmunity, Cell Adhesion, Cell Surface Extensions metabolism, Fibronectins metabolism, HLA-DR Antigens metabolism, Intracellular Signaling Peptides and Proteins metabolism, Lysophosphatidylcholines metabolism, Microscopy, Video, Protein Kinase C-alpha metabolism, Protein Kinase C-delta metabolism, Syndecan-4 metabolism, Humans, Cells, Cultured, Cell Movement, Membrane Proteins metabolism, Apoptosis, Dendritic Cells immunology, Phosphorylation, Antigens, CD86 metabolism, Autoimmunity, Cell Adhesion, Cell Surface Extensions metabolism, Fibronectins metabolism, HLA-DR Antigens metabolism, Intracellular Signaling Peptides and Proteins metabolism, Lysophosphatidylcholines metabolism, Microscopy, Video, Protein Kinase C-alpha metabolism, Protein Kinase C-delta metabolism, Syndecan-4 metabolism",
author = "Johannes B{\"u}hligen and Mirko Himmel and Carl Gebhardt and Simon, {Jan C} and Wolfgang Ziegler and Marco Averbeck",
year = "2010",
language = "Deutsch",
volume = "225",
pages = "905--914",
journal = "J CELL PHYSIOL",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "3",

}

RIS

TY - JOUR

T1 - Lysophosphatidylcholine-mediated functional inactivation of syndecan-4 results in decreased adhesion and motility of dendritic cells.

AU - Bühligen, Johannes

AU - Himmel, Mirko

AU - Gebhardt, Carl

AU - Simon, Jan C

AU - Ziegler, Wolfgang

AU - Averbeck, Marco

PY - 2010

Y1 - 2010

N2 - Following antigen contact, maturation and migration of DCs into lymphatic tissues are crucial to the developing immune response or maintenance of tolerance. Lysophosphatidylcholine (LysoPC) is generated during apoptosis of cells and acts as a "find-and-eat-me" signal thought to prevent autoimmunity. Moreover, LysoPC can activate PKC and initiates a signaling cascade that leads to phosphorylation and inactivation of syndecan-4 (SDC4), a heparansulfate proteoglycan integrin co-receptor. In human monocyte-derived DCs, we recently demonstrated that SDC4 is upregulated during maturation thereby stimulating DC motility. Here, we investigate the effects of LysoPC on DC motility as well as on the involvement of PKC phosphorylation-dependent regulation of DC motility by SDC4 and PKC . Employing a static adhesion assay and videomicroscopy, we show that LysoPC inhibits adhesion of DCs to fibronectin and motility of DCs by decreasing podosome formation. Moreover, DC podosome formation and motility, which both are regulated by SDC4 and subject to control by PKC -dependent phosphorylation of SDC4, were inhibited in LysoPC-matured DCs. Thus, these DC are defective in adhesion and migration. Based on our results, we hypothesize that LysoPC released during apoptosis might delay DC migration to lymphoid organs and thus prevent autoimmunity.

AB - Following antigen contact, maturation and migration of DCs into lymphatic tissues are crucial to the developing immune response or maintenance of tolerance. Lysophosphatidylcholine (LysoPC) is generated during apoptosis of cells and acts as a "find-and-eat-me" signal thought to prevent autoimmunity. Moreover, LysoPC can activate PKC and initiates a signaling cascade that leads to phosphorylation and inactivation of syndecan-4 (SDC4), a heparansulfate proteoglycan integrin co-receptor. In human monocyte-derived DCs, we recently demonstrated that SDC4 is upregulated during maturation thereby stimulating DC motility. Here, we investigate the effects of LysoPC on DC motility as well as on the involvement of PKC phosphorylation-dependent regulation of DC motility by SDC4 and PKC . Employing a static adhesion assay and videomicroscopy, we show that LysoPC inhibits adhesion of DCs to fibronectin and motility of DCs by decreasing podosome formation. Moreover, DC podosome formation and motility, which both are regulated by SDC4 and subject to control by PKC -dependent phosphorylation of SDC4, were inhibited in LysoPC-matured DCs. Thus, these DC are defective in adhesion and migration. Based on our results, we hypothesize that LysoPC released during apoptosis might delay DC migration to lymphoid organs and thus prevent autoimmunity.

KW - Humans

KW - Cells, Cultured

KW - Cell Movement

KW - Membrane Proteins metabolism

KW - Apoptosis

KW - Dendritic Cells immunology

KW - Phosphorylation

KW - Antigens, CD86 metabolism

KW - Autoimmunity

KW - Cell Adhesion

KW - Cell Surface Extensions metabolism

KW - Fibronectins metabolism

KW - HLA-DR Antigens metabolism

KW - Intracellular Signaling Peptides and Proteins metabolism

KW - Lysophosphatidylcholines metabolism

KW - Microscopy, Video

KW - Protein Kinase C-alpha metabolism

KW - Protein Kinase C-delta metabolism

KW - Syndecan-4 metabolism

KW - Humans

KW - Cells, Cultured

KW - Cell Movement

KW - Membrane Proteins metabolism

KW - Apoptosis

KW - Dendritic Cells immunology

KW - Phosphorylation

KW - Antigens, CD86 metabolism

KW - Autoimmunity

KW - Cell Adhesion

KW - Cell Surface Extensions metabolism

KW - Fibronectins metabolism

KW - HLA-DR Antigens metabolism

KW - Intracellular Signaling Peptides and Proteins metabolism

KW - Lysophosphatidylcholines metabolism

KW - Microscopy, Video

KW - Protein Kinase C-alpha metabolism

KW - Protein Kinase C-delta metabolism

KW - Syndecan-4 metabolism

M3 - SCORING: Zeitschriftenaufsatz

VL - 225

SP - 905

EP - 914

JO - J CELL PHYSIOL

JF - J CELL PHYSIOL

SN - 0021-9541

IS - 3

M1 - 3

ER -