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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">An important role of lymphatic vessel activation in limiting acute inflammation</title>
<author><name sortKey="Huggenberger, Reto" sort="Huggenberger, Reto" uniqKey="Huggenberger R" first="Reto" last="Huggenberger">Reto Huggenberger</name>
<affiliation><nlm:aff wicri:cut=" and" id="aff1">Institute of Pharmaceutical Sciences</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Siddiqui, Shoib S" sort="Siddiqui, Shoib S" uniqKey="Siddiqui S" first="Shoib S." last="Siddiqui">Shoib S. Siddiqui</name>
<affiliation><nlm:aff wicri:cut=" and" id="aff1">Institute of Pharmaceutical Sciences</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brander, Daniela" sort="Brander, Daniela" uniqKey="Brander D" first="Daniela" last="Brander">Daniela Brander</name>
<affiliation><nlm:aff wicri:cut=" and" id="aff1">Institute of Pharmaceutical Sciences</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ullmann, Stefan" sort="Ullmann, Stefan" uniqKey="Ullmann S" first="Stefan" last="Ullmann">Stefan Ullmann</name>
<affiliation><nlm:aff wicri:cut=" and" id="aff1">Institute of Pharmaceutical Sciences</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zimmermann, Kathrin" sort="Zimmermann, Kathrin" uniqKey="Zimmermann K" first="Kathrin" last="Zimmermann">Kathrin Zimmermann</name>
<affiliation><nlm:aff wicri:cut=" and" id="aff1">Institute of Pharmaceutical Sciences</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Antsiferova, Maria" sort="Antsiferova, Maria" uniqKey="Antsiferova M" first="Maria" last="Antsiferova">Maria Antsiferova</name>
<affiliation><nlm:aff wicri:cut="; and" id="aff2">Institute of Cell Biology, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Werner, Sabine" sort="Werner, Sabine" uniqKey="Werner S" first="Sabine" last="Werner">Sabine Werner</name>
<affiliation><nlm:aff wicri:cut="; and" id="aff2">Institute of Cell Biology, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name>
<affiliation><nlm:aff id="aff3">Molecular/Cancer Biology Laboratory, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name>
<affiliation><nlm:aff wicri:cut=" and" id="aff1">Institute of Pharmaceutical Sciences</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">21364190</idno>
<idno type="pmc">3099581</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3099581</idno>
<idno type="RBID">PMC:3099581</idno>
<idno type="doi">10.1182/blood-2010-10-316356</idno>
<date when="2011">2011</date>
<idno type="wicri:Area/Pmc/Corpus">002C66</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002C66</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">An important role of lymphatic vessel activation in limiting acute inflammation</title>
<author><name sortKey="Huggenberger, Reto" sort="Huggenberger, Reto" uniqKey="Huggenberger R" first="Reto" last="Huggenberger">Reto Huggenberger</name>
<affiliation><nlm:aff wicri:cut=" and" id="aff1">Institute of Pharmaceutical Sciences</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Siddiqui, Shoib S" sort="Siddiqui, Shoib S" uniqKey="Siddiqui S" first="Shoib S." last="Siddiqui">Shoib S. Siddiqui</name>
<affiliation><nlm:aff wicri:cut=" and" id="aff1">Institute of Pharmaceutical Sciences</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brander, Daniela" sort="Brander, Daniela" uniqKey="Brander D" first="Daniela" last="Brander">Daniela Brander</name>
<affiliation><nlm:aff wicri:cut=" and" id="aff1">Institute of Pharmaceutical Sciences</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ullmann, Stefan" sort="Ullmann, Stefan" uniqKey="Ullmann S" first="Stefan" last="Ullmann">Stefan Ullmann</name>
<affiliation><nlm:aff wicri:cut=" and" id="aff1">Institute of Pharmaceutical Sciences</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Zimmermann, Kathrin" sort="Zimmermann, Kathrin" uniqKey="Zimmermann K" first="Kathrin" last="Zimmermann">Kathrin Zimmermann</name>
<affiliation><nlm:aff wicri:cut=" and" id="aff1">Institute of Pharmaceutical Sciences</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Antsiferova, Maria" sort="Antsiferova, Maria" uniqKey="Antsiferova M" first="Maria" last="Antsiferova">Maria Antsiferova</name>
<affiliation><nlm:aff wicri:cut="; and" id="aff2">Institute of Cell Biology, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Werner, Sabine" sort="Werner, Sabine" uniqKey="Werner S" first="Sabine" last="Werner">Sabine Werner</name>
<affiliation><nlm:aff wicri:cut="; and" id="aff2">Institute of Cell Biology, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name>
<affiliation><nlm:aff id="aff3">Molecular/Cancer Biology Laboratory, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Detmar, Michael" sort="Detmar, Michael" uniqKey="Detmar M" first="Michael" last="Detmar">Michael Detmar</name>
<affiliation><nlm:aff wicri:cut=" and" id="aff1">Institute of Pharmaceutical Sciences</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">Blood</title>
<idno type="ISSN">0006-4971</idno>
<idno type="eISSN">1528-0020</idno>
<imprint><date when="2011">2011</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>In contrast to the established role of blood vessel remodeling in inflammation, the biologic function of the lymphatic vasculature in acute inflammation has remained less explored. We studied 2 established models of acute cutaneous inflammation, namely, oxazolone-induced delayed-type hypersensitivity reactions and ultraviolet B irradiation, in keratin 14-vascular endothelial growth factor (VEGF)-C and keratin 14-VEGF-D transgenic mice. These mice have an expanded network of cutaneous lymphatic vessels. Transgenic delivery of the lymphangiogenic factors VEGF-C and the VEGFR-3 specific ligand mouse VEGF-D significantly limited acute skin inflammation in both experimental models, with a strong reduction of dermal edema. Expression of VEGFR-3 by lymphatic endothelium was strongly down-regulated at the mRNA and protein level in acutely inflamed skin, and no VEGFR-3 expression was detectable on inflamed blood vessels and dermal macrophages. There was no major change of the inflammatory cell infiltrate or the composition of the inflammatory cytokine milieu in the inflamed skin of VEGF-C or VEGF-D transgenic mice. However, the increased network of lymphatic vessels in these mice significantly enhanced lymphatic drainage from the ear skin. These results provide evidence that specific lymphatic vessel activation limits acute skin inflammation via promotion of lymph flow from the skin and reduction of edema formation.</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">Blood</journal-id>
<journal-id journal-id-type="hwp">bloodjournal</journal-id>
<journal-id journal-id-type="pmc">blood</journal-id>
<journal-id journal-id-type="publisher-id">Blood</journal-id>
<journal-title-group><journal-title>Blood</journal-title>
</journal-title-group>
<issn pub-type="ppub">0006-4971</issn>
<issn pub-type="epub">1528-0020</issn>
<publisher><publisher-name>American Society of Hematology</publisher-name>
<publisher-loc>Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21364190</article-id>
<article-id pub-id-type="pmc">3099581</article-id>
<article-id pub-id-type="publisher-id">2010/316356</article-id>
<article-id pub-id-type="doi">10.1182/blood-2010-10-316356</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Vascular Biology</subject>
</subj-group>
</article-categories>
<title-group><article-title>An important role of lymphatic vessel activation in limiting acute inflammation</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Huggenberger</surname>
<given-names>Reto</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Siddiqui</surname>
<given-names>Shoib S.</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brander</surname>
<given-names>Daniela</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ullmann</surname>
<given-names>Stefan</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zimmermann</surname>
<given-names>Kathrin</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Antsiferova</surname>
<given-names>Maria</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Werner</surname>
<given-names>Sabine</given-names>
</name>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Alitalo</surname>
<given-names>Kari</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Detmar</surname>
<given-names>Michael</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<aff id="aff1"><label>1</label>
Institute of Pharmaceutical Sciences and</aff>
<aff id="aff2"><label>2</label>
Institute of Cell Biology, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland; and</aff>
<aff id="aff3"><label>3</label>
Molecular/Cancer Biology Laboratory, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland</aff>
</contrib-group>
<pub-date pub-type="ppub"><day>28</day>
<month>4</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="epreprint"><day>1</day>
<month>3</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>28</day>
<month>4</month>
<year>2012</year>
</pub-date>
<pmc-comment> PMC Release delay is 12 months and 0 days and was based on the
. </pmc-comment>
<volume>117</volume>
<issue>17</issue>
<fpage>4667</fpage>
<lpage>4678</lpage>
<history><date date-type="received"><day>28</day>
<month>10</month>
<year>2010</year>
</date>
<date date-type="accepted"><day>14</day>
<month>2</month>
<year>2011</year>
</date>
</history>
<permissions><copyright-statement>© 2011 by The American Society of Hematology</copyright-statement>
<copyright-year>2011</copyright-year>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zh801711004667.pdf"></self-uri>
<abstract><p>In contrast to the established role of blood vessel remodeling in inflammation, the biologic function of the lymphatic vasculature in acute inflammation has remained less explored. We studied 2 established models of acute cutaneous inflammation, namely, oxazolone-induced delayed-type hypersensitivity reactions and ultraviolet B irradiation, in keratin 14-vascular endothelial growth factor (VEGF)-C and keratin 14-VEGF-D transgenic mice. These mice have an expanded network of cutaneous lymphatic vessels. Transgenic delivery of the lymphangiogenic factors VEGF-C and the VEGFR-3 specific ligand mouse VEGF-D significantly limited acute skin inflammation in both experimental models, with a strong reduction of dermal edema. Expression of VEGFR-3 by lymphatic endothelium was strongly down-regulated at the mRNA and protein level in acutely inflamed skin, and no VEGFR-3 expression was detectable on inflamed blood vessels and dermal macrophages. There was no major change of the inflammatory cell infiltrate or the composition of the inflammatory cytokine milieu in the inflamed skin of VEGF-C or VEGF-D transgenic mice. However, the increased network of lymphatic vessels in these mice significantly enhanced lymphatic drainage from the ear skin. These results provide evidence that specific lymphatic vessel activation limits acute skin inflammation via promotion of lymph flow from the skin and reduction of edema formation.</p>
</abstract>
<funding-group><award-group><funding-source id="CS100">National Institutes of Health</funding-source>
<award-id rid="CS100">CA69184</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>
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