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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Impaired lymphatic contraction associated with immunosuppression</title><author><name sortKey="Liao, Shan" sort="Liao, Shan" uniqKey="Liao S" first="Shan" last="Liao">Shan Liao</name><affiliation><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff></affiliation></author><author><name sortKey="Cheng, Gang" sort="Cheng, Gang" uniqKey="Cheng G" first="Gang" last="Cheng">Gang Cheng</name><affiliation><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff></affiliation></author><author><name sortKey="Conner, David A" sort="Conner, David A" uniqKey="Conner D" first="David A." last="Conner">David A. Conner</name><affiliation><nlm:aff wicri:cut="; and" id="aff2">Department of Genetics,<institution>Brigham and Women's Hospital</institution>, Boston, MA 02115</nlm:aff></affiliation></author><author><name sortKey="Huang, Yuhui" sort="Huang, Yuhui" uniqKey="Huang Y" first="Yuhui" last="Huang">Yuhui Huang</name><affiliation><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff></affiliation></author><author><name sortKey="Kucherlapati, Raju S" sort="Kucherlapati, Raju S" uniqKey="Kucherlapati R" first="Raju S." last="Kucherlapati">Raju S. Kucherlapati</name><affiliation><nlm:aff wicri:cut="; and" id="aff2">Department of Genetics,<institution>Brigham and Women's Hospital</institution>, Boston, MA 02115</nlm:aff></affiliation></author><author><name sortKey="Munn, Lance L" sort="Munn, Lance L" uniqKey="Munn L" first="Lance L." last="Munn">Lance L. Munn</name><affiliation><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff></affiliation></author><author><name sortKey="Ruddle, Nancy H" sort="Ruddle, Nancy H" uniqKey="Ruddle N" first="Nancy H." last="Ruddle">Nancy H. Ruddle</name><affiliation><nlm:aff id="aff3">Departments of Epidemiology and Public Health and Immunobiology,<institution>Yale University School of Medicine</institution>, New Haven, CT 06511</nlm:aff></affiliation></author><author><name sortKey="Jain, Rakesh K" sort="Jain, Rakesh K" uniqKey="Jain R" first="Rakesh K." last="Jain">Rakesh K. Jain</name><affiliation><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff></affiliation></author><author><name sortKey="Fukumura, Dai" sort="Fukumura, Dai" uniqKey="Fukumura D" first="Dai" last="Fukumura">Dai Fukumura</name><affiliation><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff></affiliation></author><author><name sortKey="Padera, Timothy P" sort="Padera, Timothy P" uniqKey="Padera T" first="Timothy P." last="Padera">Timothy P. Padera</name><affiliation><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22065738</idno><idno type="pmc">3219138</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219138</idno><idno type="RBID">PMC:3219138</idno><idno type="doi">10.1073/pnas.1116152108</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">003166</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003166</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Impaired lymphatic contraction associated with immunosuppression</title><author><name sortKey="Liao, Shan" sort="Liao, Shan" uniqKey="Liao S" first="Shan" last="Liao">Shan Liao</name><affiliation><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff></affiliation></author><author><name sortKey="Cheng, Gang" sort="Cheng, Gang" uniqKey="Cheng G" first="Gang" last="Cheng">Gang Cheng</name><affiliation><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff></affiliation></author><author><name sortKey="Conner, David A" sort="Conner, David A" uniqKey="Conner D" first="David A." last="Conner">David A. Conner</name><affiliation><nlm:aff wicri:cut="; and" id="aff2">Department of Genetics,<institution>Brigham and Women's Hospital</institution>, Boston, MA 02115</nlm:aff></affiliation></author><author><name sortKey="Huang, Yuhui" sort="Huang, Yuhui" uniqKey="Huang Y" first="Yuhui" last="Huang">Yuhui Huang</name><affiliation><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff></affiliation></author><author><name sortKey="Kucherlapati, Raju S" sort="Kucherlapati, Raju S" uniqKey="Kucherlapati R" first="Raju S." last="Kucherlapati">Raju S. Kucherlapati</name><affiliation><nlm:aff wicri:cut="; and" id="aff2">Department of Genetics,<institution>Brigham and Women's Hospital</institution>, Boston, MA 02115</nlm:aff></affiliation></author><author><name sortKey="Munn, Lance L" sort="Munn, Lance L" uniqKey="Munn L" first="Lance L." last="Munn">Lance L. Munn</name><affiliation><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff></affiliation></author><author><name sortKey="Ruddle, Nancy H" sort="Ruddle, Nancy H" uniqKey="Ruddle N" first="Nancy H." last="Ruddle">Nancy H. Ruddle</name><affiliation><nlm:aff id="aff3">Departments of Epidemiology and Public Health and Immunobiology,<institution>Yale University School of Medicine</institution>, New Haven, CT 06511</nlm:aff></affiliation></author><author><name sortKey="Jain, Rakesh K" sort="Jain, Rakesh K" uniqKey="Jain R" first="Rakesh K." last="Jain">Rakesh K. Jain</name><affiliation><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff></affiliation></author><author><name sortKey="Fukumura, Dai" sort="Fukumura, Dai" uniqKey="Fukumura D" first="Dai" last="Fukumura">Dai Fukumura</name><affiliation><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff></affiliation></author><author><name sortKey="Padera, Timothy P" sort="Padera, Timothy P" uniqKey="Padera T" first="Timothy P." last="Padera">Timothy P. Padera</name><affiliation><nlm:aff wicri:cut=" and" id="aff1">E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</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>To trigger an effective immune response, antigen and antigen-presenting cells travel to the lymph nodes via collecting lymphatic vessels. However, our understanding of the regulation of collecting lymphatic vessel function and lymph transport is limited. To dissect the molecular control of lymphatic function, we developed a unique mouse model that allows intravital imaging of autonomous lymphatic vessel contraction. Using this method, we demonstrated that endothelial nitric oxide synthase (eNOS) in lymphatic endothelial cells is required for robust lymphatic contractions under physiological conditions. By contrast, under inflammatory conditions, inducible NOS (iNOS)-expressing CD11b<sup>+</sup>Gr-1<sup>+</sup> cells attenuate lymphatic contraction. This inhibition of lymphatic contraction was associated with a reduction in the response to antigen in a model of immune-induced multiple sclerosis. These results suggest the suppression of lymphatic function by the CD11b<sup>+</sup>Gr-1<sup>+</sup> cells as a potential mechanism of self-protection from autoreactive responses during on-going inflammation. The central role for nitric oxide also suggests that other diseases such as cancer and infection may also mediate lymphatic contraction and thus immune response. Our unique method allows the study of lymphatic function and its molecular regulation during inflammation, lymphedema, and lymphatic metastasis.</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">Proc Natl Acad Sci U S A</journal-id><journal-id journal-id-type="hwp">pnas</journal-id><journal-id journal-id-type="pmc">pnas</journal-id><journal-id journal-id-type="publisher-id">PNAS</journal-id><journal-title-group><journal-title>Proceedings of the National Academy of Sciences of the United States of America</journal-title></journal-title-group><issn pub-type="ppub">0027-8424</issn><issn pub-type="epub">1091-6490</issn><publisher><publisher-name>National Academy of Sciences</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">22065738</article-id><article-id pub-id-type="pmc">3219138</article-id><article-id pub-id-type="publisher-id">201116152</article-id><article-id pub-id-type="doi">10.1073/pnas.1116152108</article-id><article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject><subj-group><subject>Medical Sciences</subject></subj-group></subj-group><subj-group subj-group-type="heading"><subject>Physical Sciences</subject><subj-group><subject>Engineering</subject></subj-group></subj-group></article-categories><title-group><article-title>Impaired lymphatic contraction associated with immunosuppression</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Liao</surname><given-names>Shan</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Cheng</surname><given-names>Gang</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Conner</surname><given-names>David A.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Huang</surname><given-names>Yuhui</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kucherlapati</surname><given-names>Raju S.</given-names></name><xref ref-type="aff" rid="aff2"><sup>b</sup></xref></contrib><contrib contrib-type="author"><name><surname>Munn</surname><given-names>Lance L.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref></contrib><contrib contrib-type="author"><name><surname>Ruddle</surname><given-names>Nancy H.</given-names></name><xref ref-type="aff" rid="aff3"><sup>c</sup></xref></contrib><contrib contrib-type="author"><name><surname>Jain</surname><given-names>Rakesh K.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Fukumura</surname><given-names>Dai</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Padera</surname><given-names>Timothy P.</given-names></name><xref ref-type="aff" rid="aff1"><sup>a</sup></xref><xref ref-type="corresp" rid="cor1"><sup>1</sup></xref></contrib><aff id="aff1"><sup>a</sup>E. L. Steele Laboratory, Department of Radiation Oncology, Harvard Medical School and<institution>Massachusetts General Hospital</institution>, Boston, MA 02114;</aff><aff id="aff2"><sup>b</sup>Department of Genetics,<institution>Brigham and Women's Hospital</institution>, Boston, MA 02115; and</aff><aff id="aff3"><sup>c</sup>Departments of Epidemiology and Public Health and Immunobiology,<institution>Yale University School of Medicine</institution>, New Haven, CT 06511</aff></contrib-group><author-notes><corresp id="cor1"><sup>1</sup>To whom correspondence may be addressed. E-mail: <email>jain@steele.mgh.harvard.edu</email>, <email>dai@steele.mgh.harvard.edu</email>, or <email>tpadera@steele.mgh.harvard.edu</email>.</corresp><fn fn-type="edited-by"><p>Contributed by Rakesh K. Jain, October 6, 2011 (sent for review September 10, 2011)</p></fn><fn fn-type="con"><p>Author contributions: S.L., G.C., Y.H., L.L.M., N.H.R., R.K.J., D.F., and T.P.P. designed research; S.L., G.C., Y.H., N.H.R., and T.P.P. performed research; S.L., G.C., D.A.C., R.S.K., L.L.M., and T.P.P. contributed new reagents/analytic tools; S.L., G.C., Y.H., L.L.M., N.H.R., and T.P.P. analyzed data; and S.L., R.K.J., and T.P.P. wrote the paper.</p></fn></author-notes><pub-date pub-type="ppub"><day>15</day><month>11</month><year>2011</year></pub-date><pub-date pub-type="epub"><day>7</day><month>11</month><year>2011</year></pub-date><volume>108</volume><issue>46</issue><fpage>18784</fpage><lpage>18789</lpage><self-uri xlink:title="pdf" xlink:type="simple" xlink:href="pnas.201116152.pdf"></self-uri><abstract><p>To trigger an effective immune response, antigen and antigen-presenting cells travel to the lymph nodes via collecting lymphatic vessels. However, our understanding of the regulation of collecting lymphatic vessel function and lymph transport is limited. To dissect the molecular control of lymphatic function, we developed a unique mouse model that allows intravital imaging of autonomous lymphatic vessel contraction. Using this method, we demonstrated that endothelial nitric oxide synthase (eNOS) in lymphatic endothelial cells is required for robust lymphatic contractions under physiological conditions. By contrast, under inflammatory conditions, inducible NOS (iNOS)-expressing CD11b<sup>+</sup>Gr-1<sup>+</sup> cells attenuate lymphatic contraction. This inhibition of lymphatic contraction was associated with a reduction in the response to antigen in a model of immune-induced multiple sclerosis. These results suggest the suppression of lymphatic function by the CD11b<sup>+</sup>Gr-1<sup>+</sup> cells as a potential mechanism of self-protection from autoreactive responses during on-going inflammation. The central role for nitric oxide also suggests that other diseases such as cancer and infection may also mediate lymphatic contraction and thus immune response. Our unique method allows the study of lymphatic function and its molecular regulation during inflammation, lymphedema, and lymphatic metastasis.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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