Novel Expression of Vascular Endothelial Growth Factor Receptor (VEGFR)-3 and VEGF-C on Corneal Dendritic Cells
Identifieur interne : 000D85 ( Ncbi/Merge ); précédent : 000D84; suivant : 000D86Novel Expression of Vascular Endothelial Growth Factor Receptor (VEGFR)-3 and VEGF-C on Corneal Dendritic Cells
Auteurs : Pedram Hamrah ; Lu Chen ; Qiang Zhang ; M. Reza DanaSource :
- The American Journal of Pathology [ 0002-9440 ] ; 2003.
Abstract
Vascular endothelial growth factor-3 (VEGFR-3) plays a critical role in embryonic cardiovascular development and is thought to be expressed exclusively on the lymphatic endothelium, high endothelial venules, and rarely on adult vascular endothelium. Recent evidence also suggests expression of VEGFR-3 on some tumor-associated macrophages. We have studied the expression of VEGFR-3, its ligand VEGF-C and the co-receptor neuropilin-2, in normal and inflamed corneas and characterized the phenotype and distribution of VEGFR-3+ cells. Our data demonstrate, for the first time, the expression of VEGFR-3 on corneal dendritic cells (DC) and its up-regulation in inflammation. VEGFR-3+ DC are CD11c+CD45+CD11b+, and are mostly major histocompatibility (MHC) class II−CD80−CD86−, indicating immature DC of a monocytic lineage. During inflammation, there is rapid increase in the number of VEGFR-3+ DC in the cornea associated with heightened membranous expression as compared to a mostly intracellular expression in uninflamed tissue. VEGFR-3+ DC in normal corneas are VEGF-C−neuropilin-2−, but express VEGF-C in inflammation. Interestingly, similar cells are absent both in the normal and inflamed skin. These data demonstrate, for the first time, the expression of VEGFR-3 and VEGF-C on tissue DC, which implicate a novel potential relationship between lymphangiogenesis and leukocyte trafficking in the eye.
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PubMed: 12819011
PubMed Central: 1868166
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Novel Expression of Vascular Endothelial Growth Factor Receptor (VEGFR)-3 and VEGF-C on Corneal Dendritic Cells</title><author><name sortKey="Hamrah, Pedram" sort="Hamrah, Pedram" uniqKey="Hamrah P" first="Pedram" last="Hamrah">Pedram Hamrah</name></author><author><name sortKey="Chen, Lu" sort="Chen, Lu" uniqKey="Chen L" first="Lu" last="Chen">Lu Chen</name></author><author><name sortKey="Zhang, Qiang" sort="Zhang, Qiang" uniqKey="Zhang Q" first="Qiang" last="Zhang">Qiang Zhang</name></author><author><name sortKey="Dana, M Reza" sort="Dana, M Reza" uniqKey="Dana M" first="M. Reza" last="Dana">M. Reza Dana</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">12819011</idno><idno type="pmc">1868166</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868166</idno><idno type="RBID">PMC:1868166</idno><date when="2003">2003</date><idno type="wicri:Area/Pmc/Corpus">001263</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001263</idno><idno type="wicri:Area/Pmc/Curation">001262</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001262</idno><idno type="wicri:Area/Pmc/Checkpoint">003E85</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">003E85</idno><idno type="wicri:Area/Ncbi/Merge">000D85</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Novel Expression of Vascular Endothelial Growth Factor Receptor (VEGFR)-3 and VEGF-C on Corneal Dendritic Cells</title><author><name sortKey="Hamrah, Pedram" sort="Hamrah, Pedram" uniqKey="Hamrah P" first="Pedram" last="Hamrah">Pedram Hamrah</name></author><author><name sortKey="Chen, Lu" sort="Chen, Lu" uniqKey="Chen L" first="Lu" last="Chen">Lu Chen</name></author><author><name sortKey="Zhang, Qiang" sort="Zhang, Qiang" uniqKey="Zhang Q" first="Qiang" last="Zhang">Qiang Zhang</name></author><author><name sortKey="Dana, M Reza" sort="Dana, M Reza" uniqKey="Dana M" first="M. Reza" last="Dana">M. Reza Dana</name></author></analytic><series><title level="j">The American Journal of Pathology</title><idno type="ISSN">0002-9440</idno><idno type="eISSN">1525-2191</idno><imprint><date when="2003">2003</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Vascular endothelial growth factor-3 (VEGFR-3) plays a critical role in embryonic cardiovascular development and is thought to be expressed exclusively on the lymphatic endothelium, high endothelial venules, and rarely on adult vascular endothelium. Recent evidence also suggests expression of VEGFR-3 on some tumor-associated macrophages. We have studied the expression of VEGFR-3, its ligand VEGF-C and the co-receptor neuropilin-2, in normal and inflamed corneas and characterized the phenotype and distribution of VEGFR-3<sup>+</sup> cells. Our data demonstrate, for the first time, the expression of VEGFR-3 on corneal dendritic cells (DC) and its up-regulation in inflammation. VEGFR-3<sup>+</sup> DC are CD11c<sup>+</sup>CD45<sup>+</sup>CD11b<sup>+</sup>, and are mostly major histocompatibility (MHC) class II<sup>−</sup>CD80<sup>−</sup>CD86<sup>−</sup>, indicating immature DC of a monocytic lineage. During inflammation, there is rapid increase in the number of VEGFR-3<sup>+</sup> DC in the cornea associated with heightened membranous expression as compared to a mostly intracellular expression in uninflamed tissue. VEGFR-3<sup>+</sup> DC in normal corneas are VEGF-C<sup>−</sup>neuropilin-2<sup>−</sup>, but express VEGF-C in inflammation. Interestingly, similar cells are absent both in the normal and inflamed skin. These data demonstrate, for the first time, the expression of VEGFR-3 and VEGF-C on tissue DC, which implicate a novel potential relationship between lymphangiogenesis and leukocyte trafficking in the eye.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Pathol</journal-id><journal-id journal-id-type="publisher-id">amjpathol</journal-id><journal-title>The American Journal of Pathology</journal-title><issn pub-type="ppub">0002-9440</issn><issn pub-type="epub">1525-2191</issn><publisher><publisher-name>American Society for Investigative Pathology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">12819011</article-id><article-id pub-id-type="pmc">1868166</article-id><article-id pub-id-type="publisher-id">3663</article-id><article-categories><subj-group subj-group-type="heading"><subject>Regular Articles</subject></subj-group></article-categories><title-group><article-title>Novel Expression of Vascular Endothelial Growth Factor Receptor (VEGFR)-3 and VEGF-C on Corneal Dendritic Cells</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Hamrah</surname><given-names>Pedram</given-names></name></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Lu</given-names></name></contrib><contrib contrib-type="author"><name><surname>Zhang</surname><given-names>Qiang</given-names></name></contrib><contrib contrib-type="author"><name><surname>Dana</surname><given-names>M. Reza</given-names></name></contrib></contrib-group><aff id="N0x1f24b10N0x40824d8">From the Laboratory of Immunology, Schepens Eye Research Institute and the Massachusetts Eye and Ear Infirmary and Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts</aff><pub-date pub-type="ppub"><month>7</month><year>2003</year></pub-date><volume>163</volume><issue>1</issue><fpage>57</fpage><lpage>68</lpage><history><date date-type="accepted"><day>18</day><month>3</month><year>2003</year></date></history><permissions><copyright-statement>Copyright © 2003, American Society for Investigative Pathology</copyright-statement></permissions><abstract><p>Vascular endothelial growth factor-3 (VEGFR-3) plays a critical role in embryonic cardiovascular development and is thought to be expressed exclusively on the lymphatic endothelium, high endothelial venules, and rarely on adult vascular endothelium. Recent evidence also suggests expression of VEGFR-3 on some tumor-associated macrophages. We have studied the expression of VEGFR-3, its ligand VEGF-C and the co-receptor neuropilin-2, in normal and inflamed corneas and characterized the phenotype and distribution of VEGFR-3<sup>+</sup> cells. Our data demonstrate, for the first time, the expression of VEGFR-3 on corneal dendritic cells (DC) and its up-regulation in inflammation. VEGFR-3<sup>+</sup> DC are CD11c<sup>+</sup>CD45<sup>+</sup>CD11b<sup>+</sup>, and are mostly major histocompatibility (MHC) class II<sup>−</sup>CD80<sup>−</sup>CD86<sup>−</sup>, indicating immature DC of a monocytic lineage. During inflammation, there is rapid increase in the number of VEGFR-3<sup>+</sup> DC in the cornea associated with heightened membranous expression as compared to a mostly intracellular expression in uninflamed tissue. VEGFR-3<sup>+</sup> DC in normal corneas are VEGF-C<sup>−</sup>neuropilin-2<sup>−</sup>, but express VEGF-C in inflammation. Interestingly, similar cells are absent both in the normal and inflamed skin. These data demonstrate, for the first time, the expression of VEGFR-3 and VEGF-C on tissue DC, which implicate a novel potential relationship between lymphangiogenesis and leukocyte trafficking in the eye.</p></abstract></article-meta></front><floats-wrap><fig position="float" id="f1"><label>Figure 1.</label><caption><p>VEGFR-3 expression on cells in the periphery of the corneal stroma. Confocal micrographs demonstrate VEGFR-3<sup>+</sup> dendritic shaped cellular structures in the periphery (<bold>right</bold>) of the cornea, while the central areas (<bold>left</bold>) do not demonstrate such cells (<bold>A</bold>). Higher magnification, confirming the dendritic morphology of VEGFR-3<sup>+</sup> cells in the cornea (<bold>B</bold>). Magnification, (<bold>A</bold>) ×200, (<bold>B</bold>) ×1000.</p></caption><graphic xlink:href="jh0733663001"></graphic></fig><fig position="float" id="f2"><label>Figure 2.</label><caption><p>VEGFR-3 expression by dendritiform cells in the corneal stroma. Micrograph of double-stained cornea staining VEGFR-3 (red) and YOYO-1 (green) expression. Significant numbers of dendritic VEGFR-3<sup>+</sup> cells (<bold>arrows</bold>) are present in the corneal stroma; these cells are nucleated (yellow) and are present amid VEGFR-3<sup>−</sup> cells (green). Magnification, ×400.</p></caption><graphic xlink:href="jh0733663002"></graphic></fig><fig position="float" id="f3"><label>Figure 3.</label><caption><p>Myeloid dendritic cells in the corneal stroma express VEGFR-3. Whole-mounted corneas were double-stained with CD45 (green) and VEGFR-3 (red). Confocal micrograph of the anterior stroma shows VEGFR-3<sup>+</sup> dendritic cells being CD45<sup>+</sup> (yellow) (<bold>A</bold>). CD11c (red) expression of these VEGFR-3<sup>+</sup> (green) cells provides evidence that they are dendritic cells, and that VEGFR-3 expression is limited to the periphery of the cornea (<bold>right</bold>), while corneal DC in central areas (red) are VEGFR-3<sup>−</sup> (<bold>lower left</bold>) (<bold>B</bold>). Additionally, CD11b expression (green) of VEGFR-3<sup>+</sup> cells indicates the monocytic lineage of these cells (<bold>C</bold>). Magnification, (<bold>A</bold> and <bold>C</bold>) ×400. (<bold>B</bold>) ×160.</p></caption><graphic xlink:href="jh0733663003"></graphic></fig><fig position="float" id="f4"><label>Figure 4.</label><caption><p>Immature VEGFR-3<sup>+</sup> DC are present throughout the inflamed cornea. Stacked optical sections of the anterior stroma show that the majority of VEGFR-3<sup>+</sup> DC (red) do not express MHC class II (green) in normal corneas, and are exclusively located in the peripheral cornea (<bold>A</bold>). During inflammation, VEGFR-3<sup>+</sup> DC (red) are also present in the corneal center as early as 72 hours after induction of inflammation, but are mostly negative for MHC class II (green) expression (<bold>B</bold>). Corneas double-stained with VEGFR-3 (red) and CD80 (green) show that VEGFR-3<sup>+</sup> cells are mostly CD80<sup>−</sup> (<bold>C</bold>). After induction of inflammation, large numbers of VEGFR-3<sup>+</sup> cells are also present in the corneal center (red), but generally do not co-express the maturation marker CD80 (green) (<bold>D</bold>). Double staining with CD11c (red) and VEGFR-3 (green) in inflamed corneas shows that the VEGFR-3 expression is present both in the periphery (<bold>upper right</bold>) and the center (<bold>lower left</bold>) of the cornea and that most DC now express VEGFR-3 (yellow) (<bold>E</bold>). Double-staining of human eye bank corneal sections with VEGFR-3 (red) and HLA-DR (green) confirms the presence of VEGFR-3 on stromal cells in the human cornea (<bold>F</bold>). Magnification, (<bold>A</bold>, <bold>B</bold>, <bold>E</bold>) ×160, (<bold>C</bold>, <bold>D</bold>, <bold>F</bold>) ×400.</p></caption><graphic xlink:href="jh0733663004"></graphic></fig><fig position="float" id="f5"><label>Figure 5.</label><caption><p>VEGFR-3 expression is limited to lymphatic endothelium in normal and inflamed skin and absent on skin DC. To determine whether VEGFR-3 is also expressed on DC in the skin, we examined normal skin tissue sections that were double-stained for VEGFR-3 (red) and LYVE-1 (green) (<bold>A</bold>). VEGFR-3 was present and co-stained with LYVE-1 on lymphatic vessels (yellow), but was not expressed by leukocytes, including DC. Similar stainings with VEGFR-3 (red) and LYVE-1 (green) in inflamed skin (<bold>B</bold>) did not induce novel expression of VEGFR-3 on DC. The expression of VEGFR-3 and LYVE-1 was limited to lymphatic endothelium (yellow) that co-stained for both antibodies. Magnification, (<bold>A</bold> and <bold>B</bold>) ×200 (Epidermis is on the <bold>top</bold>).</p></caption><graphic xlink:href="jh0733663005"></graphic></fig><fig position="float" id="f6"><label>Figure 6.</label><caption><p>VEGFR-3 staining is intracellular in uninflamed corneas, but membranous in inflamed corneas. To localize the cellular expression of VEGFR-3, we stained unfixed whole-mount corneas with VEGFR-3. Unfixed tissue failed to express VEGFR-3 (<bold>A</bold>). Similar staining of acetone-fixed corneal whole-mounts, however, showed granular cytoplasmic staining as shown with serial confocal sections of a single cell (<bold>B</bold>). Staining of unfixed inflamed corneas demonstrated VEGFR-3 expression on the cell surface (<bold>C</bold>). Magnification, (<bold>A–C</bold>) ×1000.</p></caption><graphic xlink:href="jh0733663006"></graphic></fig><fig position="float" id="f7"><label>Figure 7.</label><caption><p>VEGFR-3<sup>+</sup> DC uniformly co-express VEGF-C during inflammation. Staining of inflamed corneal tissue with VEGFR-3 (green) and VEGF-C (red) demonstrates that VEGFR-3<sup>+</sup> DC uniformly co-express the ligand VEGF-C both in the periphery (<bold>A</bold>) and the center (<bold>B</bold>) of corneas. Magnification, (<bold>A</bold>) ×160, (<bold>B</bold>) ×400.</p></caption><graphic xlink:href="jh0733663007"></graphic></fig></floats-wrap></pmc><affiliations><list></list><tree><noCountry><name sortKey="Chen, Lu" sort="Chen, Lu" uniqKey="Chen L" first="Lu" last="Chen">Lu Chen</name><name sortKey="Dana, M Reza" sort="Dana, M Reza" uniqKey="Dana M" first="M. Reza" last="Dana">M. Reza Dana</name><name sortKey="Hamrah, Pedram" sort="Hamrah, Pedram" uniqKey="Hamrah P" first="Pedram" last="Hamrah">Pedram Hamrah</name><name sortKey="Zhang, Qiang" sort="Zhang, Qiang" uniqKey="Zhang Q" first="Qiang" last="Zhang">Qiang Zhang</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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