Abnormal lymphangiogenesis in idiopathic pulmonary fibrosis with insights into cellular and molecular mechanisms
Identifieur interne : 003829 ( Pmc/Checkpoint ); précédent : 003828; suivant : 003830Abnormal lymphangiogenesis in idiopathic pulmonary fibrosis with insights into cellular and molecular mechanisms
Auteurs : Souheil El-Chemaly ; Daniela Malide ; Enrique Zudaire [États-Unis] ; Yoshihiko Ikeda ; Benjamin A. Weinberg ; Gustavo Pacheco-Rodriguez ; Ivan O. Rosas ; Marta Aparicio [États-Unis] ; Ping Ren ; Sandra D. Macdonald ; Hai-Ping Wu ; Steven D. Nathan [États-Unis] ; Frank Cuttitta [États-Unis] ; J. Philip Mccoy [États-Unis] ; Bernadette R. Gochuico [États-Unis] ; Joel MossSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2009.
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, debilitating respiratory disease whose pathogenesis is poorly understood. In IPF, the lung parenchyma undergoes extensive remodeling. We hypothesized that lymphangiogenesis is part of lung remodeling and sought to characterize pathways leading to lymphangiogenesis in IPF. We found that the diameter of lymphatic vessels in alveolar spaces in IPF lung tissue correlated with disease severity, suggesting that the alveolar microenvironment plays a role in the lymphangiogenic process. In bronchoalveolar lavage fluid (BALF) from subjects with IPF, we found short-fragment hyaluronic acid, which induced migration and proliferation of lymphatic endothelial cells (LECs), processes required for lymphatic vessel formation. To determine the origin of LECs in IPF, we isolated macrophages from the alveolar spaces; CD11b+ macrophages from subjects with IPF, but not those from healthy volunteers, formed lymphatic-like vessels in vitro. Our findings demonstrate that in the alveolar microenvironment of IPF, soluble factors such as short-fragment hyaluronic acid and cells such as CD11b+ macrophages contribute to lymphangiogenesis. These results improve our understanding of lymphangiogenesis and tissue remodeling in IPF and perhaps other fibrotic diseases as well.
Url:
DOI: 10.1073/pnas.0813368106
PubMed: 19237567
PubMed Central: 2646625
Affiliations:
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<front><div type="abstract" xml:lang="en"><p>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, debilitating respiratory disease whose pathogenesis is poorly understood. In IPF, the lung parenchyma undergoes extensive remodeling. We hypothesized that lymphangiogenesis is part of lung remodeling and sought to characterize pathways leading to lymphangiogenesis in IPF. We found that the diameter of lymphatic vessels in alveolar spaces in IPF lung tissue correlated with disease severity, suggesting that the alveolar microenvironment plays a role in the lymphangiogenic process. In bronchoalveolar lavage fluid (BALF) from subjects with IPF, we found short-fragment hyaluronic acid, which induced migration and proliferation of lymphatic endothelial cells (LECs), processes required for lymphatic vessel formation. To determine the origin of LECs in IPF, we isolated macrophages from the alveolar spaces; CD11b<sup>+</sup>
macrophages from subjects with IPF, but not those from healthy volunteers, formed lymphatic-like vessels in vitro. Our findings demonstrate that in the alveolar microenvironment of IPF, soluble factors such as short-fragment hyaluronic acid and cells such as CD11b<sup>+</sup>
macrophages contribute to lymphangiogenesis. These results improve our understanding of lymphangiogenesis and tissue remodeling in IPF and perhaps other fibrotic diseases as well.</p>
</div>
</front>
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<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>
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<article-id pub-id-type="doi">10.1073/pnas.0813368106</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Biological Sciences</subject>
<subj-group><subject>Medical Sciences</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Abnormal lymphangiogenesis in idiopathic pulmonary fibrosis with insights into cellular and molecular mechanisms</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>El-Chemaly</surname>
<given-names>Souheil</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Malide</surname>
<given-names>Daniela</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zudaire</surname>
<given-names>Enrique</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ikeda</surname>
<given-names>Yoshihiko</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="author-notes" rid="FN1"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Weinberg</surname>
<given-names>Benjamin A.</given-names>
</name>
<xref ref-type="aff" rid="aff2"><sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pacheco-Rodriguez</surname>
<given-names>Gustavo</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rosas</surname>
<given-names>Ivan O.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="author-notes" rid="FN2"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Aparicio</surname>
<given-names>Marta</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ren</surname>
<given-names>Ping</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>MacDonald</surname>
<given-names>Sandra D.</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wu</surname>
<given-names>Hai-Ping</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nathan</surname>
<given-names>Steven D.</given-names>
</name>
<xref ref-type="aff" rid="aff5"><sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Cuttitta</surname>
<given-names>Frank</given-names>
</name>
<xref ref-type="aff" rid="aff4"><sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McCoy</surname>
<given-names>J. Philip</given-names>
</name>
<xref ref-type="aff" rid="aff3"><sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gochuico</surname>
<given-names>Bernadette R.</given-names>
</name>
<xref ref-type="aff" rid="aff6"><sup>f</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Moss</surname>
<given-names>Joel</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>a</sup>
</xref>
<xref ref-type="corresp" rid="cor1"><sup>3</sup>
</xref>
</contrib>
<aff id="aff1"><sup>a</sup>
Translational Medicine Branch,</aff>
<aff id="aff2"><sup>b</sup>
Light Microscopy Core Facility, and</aff>
<aff id="aff3"><sup>e</sup>
Flow Cytometry Core Facility, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892;</aff>
<aff id="aff4"><sup>c</sup>
Angiogenesis Core Facility, National Cancer Institute, National Institutes of Health, Gaithersburg, MD 20877;</aff>
<aff id="aff5"><sup>d</sup>
Advanced Lung Disease and Transplant Program, Inova Heart & Vascular Institute, Inova Fairfax Hospital, Falls Church, VA 22042; and</aff>
<aff id="aff6"><sup>f</sup>
Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892</aff>
</contrib-group>
<author-notes><corresp id="cor1"><sup>3</sup>
To whom correspondence should be addressed. E-mail: <email>mossj@nhlbi.nih.gov</email>
</corresp>
<fn fn-type="com"><p>Communicated by Martha Vaughan, National Heart, Lung, and Blood Institute, Bethesda, MD, December 31, 2008</p>
</fn>
<fn fn-type="con"><p>Author contributions: S.E.-C., D.M., E.Z., G.P.-R., B.R.G., and J.M. designed research; S.E.-C., D.M., E.Z., Y.I., M.A., S.D.M., F.C., J.P.M., and B.R.G. performed research; I.O.R., S.D.N., F.C., and B.R.G. contributed new reagents/analytic tools; S.E.-C., D.M., E.Z., B.A.W., G.P.-R., P.R., H.-P.W., J.P.M., and J.M. analyzed data; and S.E.-C., D.M., G.P.-R., B.R.G., and J.M. wrote the paper.</p>
</fn>
<fn id="FN1" fn-type="present-address"><p><sup>1</sup>
Present address: Department of Pathology, National Cardiovascular Center 5–7-1, Fujishirodai, Suita, Osaka 565-8565, Japan.</p>
</fn>
<fn id="FN2" fn-type="present-address"><p><sup>2</sup>
Present address: Department of Medicine, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub"><day>10</day>
<month>3</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="epub"><day>23</day>
<month>2</month>
<year>2009</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>23</day>
<month>2</month>
<year>2009</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the
epub date downloaded from Highwire. </pmc-comment>
<volume>106</volume>
<issue>10</issue>
<fpage>3958</fpage>
<lpage>3963</lpage>
<history><date date-type="received"><day>1</day>
<month>12</month>
<year>2008</year>
</date>
</history>
<permissions><copyright-statement>© 2009 by The National Academy of Sciences of the USA</copyright-statement>
<license license-type="open-access"><license-p>Freely available online through the PNAS open access option.</license-p>
</license>
</permissions>
<self-uri xlink:title="pdf" xlink:type="simple" xlink:href="zpq01009003958.pdf"></self-uri>
<abstract><p>Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, debilitating respiratory disease whose pathogenesis is poorly understood. In IPF, the lung parenchyma undergoes extensive remodeling. We hypothesized that lymphangiogenesis is part of lung remodeling and sought to characterize pathways leading to lymphangiogenesis in IPF. We found that the diameter of lymphatic vessels in alveolar spaces in IPF lung tissue correlated with disease severity, suggesting that the alveolar microenvironment plays a role in the lymphangiogenic process. In bronchoalveolar lavage fluid (BALF) from subjects with IPF, we found short-fragment hyaluronic acid, which induced migration and proliferation of lymphatic endothelial cells (LECs), processes required for lymphatic vessel formation. To determine the origin of LECs in IPF, we isolated macrophages from the alveolar spaces; CD11b<sup>+</sup>
macrophages from subjects with IPF, but not those from healthy volunteers, formed lymphatic-like vessels in vitro. Our findings demonstrate that in the alveolar microenvironment of IPF, soluble factors such as short-fragment hyaluronic acid and cells such as CD11b<sup>+</sup>
macrophages contribute to lymphangiogenesis. These results improve our understanding of lymphangiogenesis and tissue remodeling in IPF and perhaps other fibrotic diseases as well.</p>
</abstract>
<kwd-group><kwd>endothelial cell</kwd>
<kwd>hyaluronan</kwd>
<kwd>idiopathic pulmonary fibrosis</kwd>
<kwd>lymphangiogenesis</kwd>
<kwd>macrophage</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>Maryland</li>
<li>Virginie</li>
</region>
</list>
<tree><noCountry><name sortKey="El Chemaly, Souheil" sort="El Chemaly, Souheil" uniqKey="El Chemaly S" first="Souheil" last="El-Chemaly">Souheil El-Chemaly</name>
<name sortKey="Ikeda, Yoshihiko" sort="Ikeda, Yoshihiko" uniqKey="Ikeda Y" first="Yoshihiko" last="Ikeda">Yoshihiko Ikeda</name>
<name sortKey="Macdonald, Sandra D" sort="Macdonald, Sandra D" uniqKey="Macdonald S" first="Sandra D." last="Macdonald">Sandra D. Macdonald</name>
<name sortKey="Malide, Daniela" sort="Malide, Daniela" uniqKey="Malide D" first="Daniela" last="Malide">Daniela Malide</name>
<name sortKey="Moss, Joel" sort="Moss, Joel" uniqKey="Moss J" first="Joel" last="Moss">Joel Moss</name>
<name sortKey="Pacheco Rodriguez, Gustavo" sort="Pacheco Rodriguez, Gustavo" uniqKey="Pacheco Rodriguez G" first="Gustavo" last="Pacheco-Rodriguez">Gustavo Pacheco-Rodriguez</name>
<name sortKey="Ren, Ping" sort="Ren, Ping" uniqKey="Ren P" first="Ping" last="Ren">Ping Ren</name>
<name sortKey="Rosas, Ivan O" sort="Rosas, Ivan O" uniqKey="Rosas I" first="Ivan O." last="Rosas">Ivan O. Rosas</name>
<name sortKey="Weinberg, Benjamin A" sort="Weinberg, Benjamin A" uniqKey="Weinberg B" first="Benjamin A." last="Weinberg">Benjamin A. Weinberg</name>
<name sortKey="Wu, Hai Ping" sort="Wu, Hai Ping" uniqKey="Wu H" first="Hai-Ping" last="Wu">Hai-Ping Wu</name>
</noCountry>
<country name="États-Unis"><region name="Maryland"><name sortKey="Zudaire, Enrique" sort="Zudaire, Enrique" uniqKey="Zudaire E" first="Enrique" last="Zudaire">Enrique Zudaire</name>
</region>
<name sortKey="Aparicio, Marta" sort="Aparicio, Marta" uniqKey="Aparicio M" first="Marta" last="Aparicio">Marta Aparicio</name>
<name sortKey="Cuttitta, Frank" sort="Cuttitta, Frank" uniqKey="Cuttitta F" first="Frank" last="Cuttitta">Frank Cuttitta</name>
<name sortKey="Gochuico, Bernadette R" sort="Gochuico, Bernadette R" uniqKey="Gochuico B" first="Bernadette R." last="Gochuico">Bernadette R. Gochuico</name>
<name sortKey="Mccoy, J Philip" sort="Mccoy, J Philip" uniqKey="Mccoy J" first="J. Philip" last="Mccoy">J. Philip Mccoy</name>
<name sortKey="Nathan, Steven D" sort="Nathan, Steven D" uniqKey="Nathan S" first="Steven D." last="Nathan">Steven D. Nathan</name>
</country>
</tree>
</affiliations>
</record>
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