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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>In vivo</italic>
quantification of lymph viscosity and pressure in lymphatic vessels and draining lymph nodes of arthritic joints in mice</title>
<author><name sortKey="Bouta, Echoe M" sort="Bouta, Echoe M" uniqKey="Bouta E" first="Echoe M" last="Bouta">Echoe M. Bouta</name>
<affiliation><nlm:aff id="au1"><institution>Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au2"><institution>Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wood, Ronald W" sort="Wood, Ronald W" uniqKey="Wood R" first="Ronald W" last="Wood">Ronald W. Wood</name>
<affiliation><nlm:aff id="au3"><institution>Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au4"><institution>Department of Urology, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brown, Edward B" sort="Brown, Edward B" uniqKey="Brown E" first="Edward B" last="Brown">Edward B. Brown</name>
<affiliation><nlm:aff id="au2"><institution>Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au5"><institution>Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au6"><institution>Cancer Center, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rahimi, Homaira" sort="Rahimi, Homaira" uniqKey="Rahimi H" first="Homaira" last="Rahimi">Homaira Rahimi</name>
<affiliation><nlm:aff id="au1"><institution>Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au7"><institution>Department of Pediatrics, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ritchlin, Christopher T" sort="Ritchlin, Christopher T" uniqKey="Ritchlin C" first="Christopher T" last="Ritchlin">Christopher T. Ritchlin</name>
<affiliation><nlm:aff id="au1"><institution>Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au8"><institution>Division of Allergy, Immunology, Rheumatology, Department of Medicine, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schwarz, Edward M" sort="Schwarz, Edward M" uniqKey="Schwarz E" first="Edward M" last="Schwarz">Edward M. Schwarz</name>
<affiliation><nlm:aff id="au1"><institution>Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au2"><institution>Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au4"><institution>Department of Urology, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au6"><institution>Cancer Center, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au8"><institution>Division of Allergy, Immunology, Rheumatology, Department of Medicine, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au9"><institution>Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">24421350</idno>
<idno type="pmc">3961082</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3961082</idno>
<idno type="RBID">PMC:3961082</idno>
<idno type="doi">10.1113/jphysiol.2013.266700</idno>
<date when="2014">2014</date>
<idno type="wicri:Area/Pmc/Corpus">002F86</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002F86</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>In vivo</italic>
quantification of lymph viscosity and pressure in lymphatic vessels and draining lymph nodes of arthritic joints in mice</title>
<author><name sortKey="Bouta, Echoe M" sort="Bouta, Echoe M" uniqKey="Bouta E" first="Echoe M" last="Bouta">Echoe M. Bouta</name>
<affiliation><nlm:aff id="au1"><institution>Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au2"><institution>Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wood, Ronald W" sort="Wood, Ronald W" uniqKey="Wood R" first="Ronald W" last="Wood">Ronald W. Wood</name>
<affiliation><nlm:aff id="au3"><institution>Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au4"><institution>Department of Urology, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Brown, Edward B" sort="Brown, Edward B" uniqKey="Brown E" first="Edward B" last="Brown">Edward B. Brown</name>
<affiliation><nlm:aff id="au2"><institution>Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au5"><institution>Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au6"><institution>Cancer Center, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rahimi, Homaira" sort="Rahimi, Homaira" uniqKey="Rahimi H" first="Homaira" last="Rahimi">Homaira Rahimi</name>
<affiliation><nlm:aff id="au1"><institution>Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au7"><institution>Department of Pediatrics, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Ritchlin, Christopher T" sort="Ritchlin, Christopher T" uniqKey="Ritchlin C" first="Christopher T" last="Ritchlin">Christopher T. Ritchlin</name>
<affiliation><nlm:aff id="au1"><institution>Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au8"><institution>Division of Allergy, Immunology, Rheumatology, Department of Medicine, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schwarz, Edward M" sort="Schwarz, Edward M" uniqKey="Schwarz E" first="Edward M" last="Schwarz">Edward M. Schwarz</name>
<affiliation><nlm:aff id="au1"><institution>Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au2"><institution>Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au4"><institution>Department of Urology, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au6"><institution>Cancer Center, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au8"><institution>Division of Allergy, Immunology, Rheumatology, Department of Medicine, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="au9"><institution>Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">The Journal of Physiology</title>
<idno type="ISSN">0022-3751</idno>
<idno type="eISSN">1469-7793</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with episodic flares. In TNF-Tg mice, a model of inflammatory–erosive arthritis, the popliteal lymph node (PLN) enlarges during the pre-arthritic ‘expanding’ phase, and then ‘collapses’ with adjacent knee flare associated with the loss of the intrinsic lymphatic pulse. As the mechanisms responsible are unknown, we developed <italic>in vivo</italic>
methods to quantify lymph viscosity and pressure in mice with wild-type (WT), expanding and collapsed PLN. While no differences in viscosity were detected via multiphoton fluorescence recovery after photobleaching (MP-FRAP) of injected FITC-BSA, a 32.6% decrease in lymph speed was observed in vessels afferent to collapsed PLN (<italic>P</italic>
< 0.05). Direct measurement of intra-lymph node pressure (LNP) demonstrated a decrease in expanding PLN <italic>versus</italic>
WT pressure (3.41 ± 0.43 <italic>vs</italic>
. 6.86 ± 0.56 cmH<sub>2</sub>
O; <italic>P</italic>
< 0.01), which dramatically increased to 9.92 ± 1.79 cmH<sub>2</sub>
O in collapsed PLN. Lymphatic pumping pressure (LPP), measured indirectly by slowly releasing a pressurized cuff occluding indocyanine green (ICG), demonstrated an increase in vessels afferent to expanding PLN <italic>versus</italic>
WT (18.76 ± 2.34 <italic>vs</italic>
. 11.04 ± 1.47 cmH<sub>2</sub>
O; <italic>P</italic>
< 0.01), which dropped to 2.61 ± 0.72 cmH<sub>2</sub>
O (<italic>P</italic>
< 0.001) after PLN collapse. Herein, we document the first <italic>in vivo</italic>
measurements of murine lymph viscosity and lymphatic pressure, and provide evidence to support the hypothesis that lymphangiogenesis and lymphatic transport are compensatory mechanisms to prevent synovitis via increased drainage of inflamed joints. Furthermore, the decrease in lymphatic flow and loss of LPP during PLN collapse are consistent with decreased drainage from the joint during arthritic flare, and validate these biomarkers of RA progression and possibly other chronic inflammatory conditions.</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">J Physiol</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Physiol. (Lond.)</journal-id>
<journal-id journal-id-type="publisher-id">tjp</journal-id>
<journal-title-group><journal-title>The Journal of Physiology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0022-3751</issn>
<issn pub-type="epub">1469-7793</issn>
<publisher><publisher-name>Blackwell publishing Ltd</publisher-name>
<publisher-loc>Oxford, UK</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">24421350</article-id>
<article-id pub-id-type="pmc">3961082</article-id>
<article-id pub-id-type="doi">10.1113/jphysiol.2013.266700</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Cardiovascular</subject>
</subj-group>
</article-categories>
<title-group><article-title><italic>In vivo</italic>
quantification of lymph viscosity and pressure in lymphatic vessels and draining lymph nodes of arthritic joints in mice</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Bouta</surname>
<given-names>Echoe M</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="aff" rid="au2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wood</surname>
<given-names>Ronald W</given-names>
</name>
<xref ref-type="aff" rid="au3">3</xref>
<xref ref-type="aff" rid="au4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Brown</surname>
<given-names>Edward B</given-names>
</name>
<xref ref-type="aff" rid="au2">2</xref>
<xref ref-type="aff" rid="au5">5</xref>
<xref ref-type="aff" rid="au6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rahimi</surname>
<given-names>Homaira</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="aff" rid="au7">7</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ritchlin</surname>
<given-names>Christopher T</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="aff" rid="au8">8</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schwarz</surname>
<given-names>Edward M</given-names>
</name>
<xref ref-type="aff" rid="au1">1</xref>
<xref ref-type="aff" rid="au2">2</xref>
<xref ref-type="aff" rid="au4">4</xref>
<xref ref-type="aff" rid="au6">6</xref>
<xref ref-type="aff" rid="au8">8</xref>
<xref ref-type="aff" rid="au9">9</xref>
<xref ref-type="corresp" rid="cor1"></xref>
</contrib>
<aff id="au1"><label>1</label>
<institution>Center for Musculoskeletal Research, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</aff>
<aff id="au2"><label>2</label>
<institution>Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</aff>
<aff id="au3"><label>3</label>
<institution>Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</aff>
<aff id="au4"><label>4</label>
<institution>Department of Urology, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</aff>
<aff id="au5"><label>5</label>
<institution>Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</aff>
<aff id="au6"><label>6</label>
<institution>Cancer Center, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</aff>
<aff id="au7"><label>7</label>
<institution>Department of Pediatrics, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</aff>
<aff id="au8"><label>8</label>
<institution>Division of Allergy, Immunology, Rheumatology, Department of Medicine, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</aff>
<aff id="au9"><label>9</label>
<institution>Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry</institution>
<addr-line>Rochester, NY, USA</addr-line>
</aff>
</contrib-group>
<author-notes><corresp id="cor1"><bold>Corresponding author</bold>
E. M. Schwarz: The Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, NY 14642, USA. Email: <email>edward_schwarz@urmc.rochester.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub"><day>15</day>
<month>3</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>12</day>
<month>2</month>
<year>2014</year>
</pub-date>
<volume>592</volume>
<issue>Pt 6</issue>
<fpage>1213</fpage>
<lpage>1223</lpage>
<history><date date-type="received"><day>10</day>
<month>10</month>
<year>2013</year>
</date>
<date date-type="accepted"><day>07</day>
<month>1</month>
<year>2014</year>
</date>
</history>
<permissions><copyright-statement>© 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society</copyright-statement>
<copyright-year>2014</copyright-year>
</permissions>
<abstract><p>Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with episodic flares. In TNF-Tg mice, a model of inflammatory–erosive arthritis, the popliteal lymph node (PLN) enlarges during the pre-arthritic ‘expanding’ phase, and then ‘collapses’ with adjacent knee flare associated with the loss of the intrinsic lymphatic pulse. As the mechanisms responsible are unknown, we developed <italic>in vivo</italic>
methods to quantify lymph viscosity and pressure in mice with wild-type (WT), expanding and collapsed PLN. While no differences in viscosity were detected via multiphoton fluorescence recovery after photobleaching (MP-FRAP) of injected FITC-BSA, a 32.6% decrease in lymph speed was observed in vessels afferent to collapsed PLN (<italic>P</italic>
< 0.05). Direct measurement of intra-lymph node pressure (LNP) demonstrated a decrease in expanding PLN <italic>versus</italic>
WT pressure (3.41 ± 0.43 <italic>vs</italic>
. 6.86 ± 0.56 cmH<sub>2</sub>
O; <italic>P</italic>
< 0.01), which dramatically increased to 9.92 ± 1.79 cmH<sub>2</sub>
O in collapsed PLN. Lymphatic pumping pressure (LPP), measured indirectly by slowly releasing a pressurized cuff occluding indocyanine green (ICG), demonstrated an increase in vessels afferent to expanding PLN <italic>versus</italic>
WT (18.76 ± 2.34 <italic>vs</italic>
. 11.04 ± 1.47 cmH<sub>2</sub>
O; <italic>P</italic>
< 0.01), which dropped to 2.61 ± 0.72 cmH<sub>2</sub>
O (<italic>P</italic>
< 0.001) after PLN collapse. Herein, we document the first <italic>in vivo</italic>
measurements of murine lymph viscosity and lymphatic pressure, and provide evidence to support the hypothesis that lymphangiogenesis and lymphatic transport are compensatory mechanisms to prevent synovitis via increased drainage of inflamed joints. Furthermore, the decrease in lymphatic flow and loss of LPP during PLN collapse are consistent with decreased drainage from the joint during arthritic flare, and validate these biomarkers of RA progression and possibly other chronic inflammatory conditions.</p>
</abstract>
</article-meta>
</front>
</pmc>
</record>
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