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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Discontinuous LYVE-1 expression in corneal limbal lymphatics: dual function as microvalves and immunological hot spots</title><author><name sortKey="Nakao, Shintaro" sort="Nakao, Shintaro" uniqKey="Nakao S" first="Shintaro" last="Nakao">Shintaro Nakao</name><affiliation><nlm:aff id="aff1">Center for Excellence in Functional and Molecular Imaging, Brigham and Women's Hospital,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Department of Radiology</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff3">Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan</nlm:aff></affiliation></author><author><name sortKey="Zandi, Souska" sort="Zandi, Souska" uniqKey="Zandi S" first="Souska" last="Zandi">Souska Zandi</name><affiliation><nlm:aff id="aff1">Center for Excellence in Functional and Molecular Imaging, Brigham and Women's Hospital,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Department of Radiology</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff3">Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Faez, Sepideh" sort="Faez, Sepideh" uniqKey="Faez S" first="Sepideh" last="Faez">Sepideh Faez</name><affiliation><nlm:aff wicri:cut="; and" id="aff3">Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Kohno, Ri Ichiro" sort="Kohno, Ri Ichiro" uniqKey="Kohno R" first="Ri-Ichiro" last="Kohno">Ri-Ichiro Kohno</name><affiliation><nlm:aff id="aff4">Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan</nlm:aff></affiliation></author><author><name sortKey="Hafezi Moghadam, Ali" sort="Hafezi Moghadam, Ali" uniqKey="Hafezi Moghadam A" first="Ali" last="Hafezi-Moghadam">Ali Hafezi-Moghadam</name><affiliation><nlm:aff id="aff1">Center for Excellence in Functional and Molecular Imaging, Brigham and Women's Hospital,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Department of Radiology</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff3">Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22090317</idno><idno type="pmc">3290436</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3290436</idno><idno type="RBID">PMC:3290436</idno><idno type="doi">10.1096/fj.11-183897</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">002E01</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002E01</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Discontinuous LYVE-1 expression in corneal limbal lymphatics: dual function as microvalves and immunological hot spots</title><author><name sortKey="Nakao, Shintaro" sort="Nakao, Shintaro" uniqKey="Nakao S" first="Shintaro" last="Nakao">Shintaro Nakao</name><affiliation><nlm:aff id="aff1">Center for Excellence in Functional and Molecular Imaging, Brigham and Women's Hospital,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Department of Radiology</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff3">Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan</nlm:aff></affiliation></author><author><name sortKey="Zandi, Souska" sort="Zandi, Souska" uniqKey="Zandi S" first="Souska" last="Zandi">Souska Zandi</name><affiliation><nlm:aff id="aff1">Center for Excellence in Functional and Molecular Imaging, Brigham and Women's Hospital,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Department of Radiology</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff3">Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Faez, Sepideh" sort="Faez, Sepideh" uniqKey="Faez S" first="Sepideh" last="Faez">Sepideh Faez</name><affiliation><nlm:aff wicri:cut="; and" id="aff3">Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author><author><name sortKey="Kohno, Ri Ichiro" sort="Kohno, Ri Ichiro" uniqKey="Kohno R" first="Ri-Ichiro" last="Kohno">Ri-Ichiro Kohno</name><affiliation><nlm:aff id="aff4">Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan</nlm:aff></affiliation></author><author><name sortKey="Hafezi Moghadam, Ali" sort="Hafezi Moghadam, Ali" uniqKey="Hafezi Moghadam A" first="Ali" last="Hafezi-Moghadam">Ali Hafezi-Moghadam</name><affiliation><nlm:aff id="aff1">Center for Excellence in Functional and Molecular Imaging, Brigham and Women's Hospital,</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut=", and" id="aff2">Department of Radiology</nlm:aff></affiliation><affiliation><nlm:aff wicri:cut="; and" id="aff3">Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA</nlm:aff></affiliation></author></analytic><series><title level="j">The FASEB Journal</title><idno type="ISSN">0892-6638</idno><idno type="eISSN">1530-6860</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>LYVE-1<sup>+</sup> corneal lymphatics contribute to drainage and immunity. LYVE-1 is widely accepted as the most reliable lymphatic marker because of its continuous expression in lymphatic endothelium. LYVE-1 expression in corneal lymphatics has not been examined. In this study, we report intact CD31<sup>+</sup> corneal lymphatic capillary endothelial cells that do not express LYVE-1. The number of LYVE-1<sup>−</sup> gaps initially increased until 8 wk of age but was significantly reduced in aged mice. C57BL/6 mice showed a notably higher number of the LYVE-1<sup>−</sup>/CD31<sup>+</sup> lymphatic regions than BALB/c mice, which suggests a genetic predisposition for this histological feature. The LYVE-1<sup>−</sup> lymphatic gaps expressed podoplanin and VE-cadherin but not αSMA or FOXC2. Interestingly, the number of LYVE-1<sup>−</sup> gaps in FGF-2, but not VEGF-A, implanted corneas was significantly lower than in untreated corneas. Over 70% of the CD45<sup>+</sup> leukocytes were found in the proximity of the LYVE-1<sup>−</sup> gaps. Using a novel <italic>in vivo</italic> imaging technique for visualization of leukocyte migration into and out of corneal stroma, we showed reentry of extravasated leukocytes from angiogenic vessels into newly grown corneal lymphatics. This process was inhibited by VE-cadherin blockade. To date, existence of lymphatic valves in cornea is unknown. Electron microscopy showed overlapping lymphatic endothelial ends, reminiscent of microvalves in corneal lymphatics. This work introduces a novel corneal endothelial lymphatic phenotype that lacks LYVE-1. LYVE-1<sup>−</sup> lymphatic endothelium could serve as microvalves, supporting unidirectional flow, as well as immunological hot spots that facilitate reentry of stromal macropahges.—Nakao, S., Zandi, S., Faez, S., Kohno, R., Hafezi-Moghadam, A. Discontinuous LYVE-1 expression in corneal limbal lymphatics: dual function as microvalves and immunological hot spots.</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">FASEB J</journal-id><journal-id journal-id-type="iso-abbrev">FASEB J</journal-id><journal-id journal-id-type="hwp">fasebj</journal-id><journal-id journal-id-type="pmc">fasebj</journal-id><journal-id journal-id-type="publisher-id">FASEB</journal-id><journal-title-group><journal-title>The FASEB Journal</journal-title></journal-title-group><issn pub-type="ppub">0892-6638</issn><issn pub-type="epub">1530-6860</issn><publisher><publisher-name>Federation of American Societies for Experimental Biology</publisher-name><publisher-loc>Bethesda, MD, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22090317</article-id><article-id pub-id-type="pmc">3290436</article-id><article-id pub-id-type="publisher-id">11-183897</article-id><article-id pub-id-type="doi">10.1096/fj.11-183897</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Communications</subject></subj-group></article-categories><title-group><article-title>Discontinuous LYVE-1 expression in corneal limbal lymphatics: dual function as microvalves and immunological hot spots</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Nakao</surname><given-names>Shintaro</given-names></name><xref ref-type="aff" rid="aff1">*</xref><xref ref-type="aff" rid="aff2"><sup>†</sup></xref><xref ref-type="aff" rid="aff3"><sup>‡</sup></xref><xref ref-type="aff" rid="aff4"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zandi</surname><given-names>Souska</given-names></name><xref ref-type="aff" rid="aff1">*</xref><xref ref-type="aff" rid="aff2"><sup>†</sup></xref><xref ref-type="aff" rid="aff3"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Faez</surname><given-names>Sepideh</given-names></name><xref ref-type="aff" rid="aff3"><sup>‡</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kohno</surname><given-names>Ri-ichiro</given-names></name><xref ref-type="aff" rid="aff4"><sup>§</sup></xref></contrib><contrib contrib-type="author"><name><surname>Hafezi-Moghadam</surname><given-names>Ali</given-names></name><xref ref-type="aff" rid="aff1">*</xref><xref ref-type="aff" rid="aff2"><sup>†</sup></xref><xref ref-type="aff" rid="aff3"><sup>‡</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><aff id="aff1"><label>*</label>Center for Excellence in Functional and Molecular Imaging, Brigham and Women's Hospital,</aff><aff id="aff2"><label>†</label>Department of Radiology, and</aff><aff id="aff3"><label>‡</label>Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA; and</aff><aff id="aff4"><label>§</label>Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan</aff></contrib-group><author-notes><corresp id="cor1"><label>1</label> Correspondence: <addr-line>Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave., 3rd Floor, Boston, Massachusetts 02115, USA</addr-line>. E-mail: <email>ahm@bwh.harvard.edu</email></corresp></author-notes><pub-date pub-type="ppub"><month>2</month><year>2012</year></pub-date><pub-date pub-type="pmc-release"><day>1</day><month>2</month><year>2013</year></pub-date><pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
<volume>26</volume><issue>2</issue><fpage>808</fpage><lpage>817</lpage><history><date date-type="received"><day>23</day><month>2</month><year>2011</year></date><date date-type="accepted"><day>24</day><month>10</month><year>2011</year></date></history><permissions><copyright-statement>© FASEB</copyright-statement><copyright-year>2012</copyright-year></permissions><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="z3800212000808.pdf"></self-uri><abstract><p>LYVE-1<sup>+</sup> corneal lymphatics contribute to drainage and immunity. LYVE-1 is widely accepted as the most reliable lymphatic marker because of its continuous expression in lymphatic endothelium. LYVE-1 expression in corneal lymphatics has not been examined. In this study, we report intact CD31<sup>+</sup> corneal lymphatic capillary endothelial cells that do not express LYVE-1. The number of LYVE-1<sup>−</sup> gaps initially increased until 8 wk of age but was significantly reduced in aged mice. C57BL/6 mice showed a notably higher number of the LYVE-1<sup>−</sup>/CD31<sup>+</sup> lymphatic regions than BALB/c mice, which suggests a genetic predisposition for this histological feature. The LYVE-1<sup>−</sup> lymphatic gaps expressed podoplanin and VE-cadherin but not αSMA or FOXC2. Interestingly, the number of LYVE-1<sup>−</sup> gaps in FGF-2, but not VEGF-A, implanted corneas was significantly lower than in untreated corneas. Over 70% of the CD45<sup>+</sup> leukocytes were found in the proximity of the LYVE-1<sup>−</sup> gaps. Using a novel <italic>in vivo</italic> imaging technique for visualization of leukocyte migration into and out of corneal stroma, we showed reentry of extravasated leukocytes from angiogenic vessels into newly grown corneal lymphatics. This process was inhibited by VE-cadherin blockade. To date, existence of lymphatic valves in cornea is unknown. Electron microscopy showed overlapping lymphatic endothelial ends, reminiscent of microvalves in corneal lymphatics. This work introduces a novel corneal endothelial lymphatic phenotype that lacks LYVE-1. LYVE-1<sup>−</sup> lymphatic endothelium could serve as microvalves, supporting unidirectional flow, as well as immunological hot spots that facilitate reentry of stromal macropahges.—Nakao, S., Zandi, S., Faez, S., Kohno, R., Hafezi-Moghadam, A. Discontinuous LYVE-1 expression in corneal limbal lymphatics: dual function as microvalves and immunological hot spots.</p></abstract><kwd-group><kwd>lymphangiogenesis</kwd><kwd>VE-cadherin</kwd><kwd>imaging</kwd><kwd>leukocyte recruitment</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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