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, Vol. 225, No. 3, 3, 2010, p. 905-914.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -