New Model of Macrophage Acquisition of the Lymphatic Endothelial Phenotype
Identifieur interne : 002859 ( Pmc/Checkpoint ); précédent : 002858; suivant : 002860New Model of Macrophage Acquisition of the Lymphatic Endothelial Phenotype
Auteurs : Kelly L. Hall ; Lisa D. Volk-Draper ; Michael J. Flister ; Sophia RanSource :
- PLoS ONE [ 1932-6203 ] ; 2012.
Abstract
Macrophage-derived lymphatic endothelial cell progenitors (M-LECPs) contribute to new lymphatic vessel formation, but the mechanisms regulating their differentiation, recruitment, and function are poorly understood. Detailed characterization of M-LECPs is limited by low frequency
Time-course analysis of diaphragms from lipopolysaccharide (LPS)-treated mice revealed rapid mobilization of bone marrow-derived and peritoneal macrophages to the proximity of lymphatic vessels followed by widespread (∼50%) incorporation of M-LECPs into the inflamed lymphatic vasculature. A differentiation shift toward the lymphatic phenotype was found in three LPS-induced subsets of activated macrophages that were positive for VEGFR-3 and many other lymphatic-specific markers. VEGFR-3 was strongly elevated in the early stage of macrophage transition to LECPs but undetectable in M-LECPs prior to vascular integration. Similar transient pattern of VEGFR-3 expression was found in RAW264.7 macrophages activated by LPS
We present a new model for macrophage-LECP differentiation based on LPS activation of cultured RAW264.7 cells. This system designated here as the “RAW model” mimics fundamental features of endogenous M-LECPs. Unlike native LECPs, this model is unrestricted by cell numbers, heterogeneity of population, and ability to change genetic composition for experimental purposes. As such, this model can provide a valuable tool for understanding the LECP and lymphatic biology.
Url:
DOI: 10.1371/journal.pone.0031794
PubMed: 22396739
PubMed Central: 3292559
Affiliations:
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<author><name sortKey="Hall, Kelly L" sort="Hall, Kelly L" uniqKey="Hall K" first="Kelly L." last="Hall">Kelly L. Hall</name>
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<author><name sortKey="Volk Draper, Lisa D" sort="Volk Draper, Lisa D" uniqKey="Volk Draper L" first="Lisa D." last="Volk-Draper">Lisa D. Volk-Draper</name>
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<author><name sortKey="Flister, Michael J" sort="Flister, Michael J" uniqKey="Flister M" first="Michael J." last="Flister">Michael J. Flister</name>
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<author><name sortKey="Ran, Sophia" sort="Ran, Sophia" uniqKey="Ran S" first="Sophia" last="Ran">Sophia Ran</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">New Model of Macrophage Acquisition of the Lymphatic Endothelial Phenotype</title>
<author><name sortKey="Hall, Kelly L" sort="Hall, Kelly L" uniqKey="Hall K" first="Kelly L." last="Hall">Kelly L. Hall</name>
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<author><name sortKey="Volk Draper, Lisa D" sort="Volk Draper, Lisa D" uniqKey="Volk Draper L" first="Lisa D." last="Volk-Draper">Lisa D. Volk-Draper</name>
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<author><name sortKey="Flister, Michael J" sort="Flister, Michael J" uniqKey="Flister M" first="Michael J." last="Flister">Michael J. Flister</name>
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<author><name sortKey="Ran, Sophia" sort="Ran, Sophia" uniqKey="Ran S" first="Sophia" last="Ran">Sophia Ran</name>
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<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Macrophage-derived lymphatic endothelial cell progenitors (M-LECPs) contribute to new lymphatic vessel formation, but the mechanisms regulating their differentiation, recruitment, and function are poorly understood. Detailed characterization of M-LECPs is limited by low frequency <italic>in vivo</italic>
and lack of model systems allowing in-depth molecular analyses <italic>in vitro</italic>
. Our goal was to establish a cell culture model to characterize inflammation-induced macrophage-to-LECP differentiation under controlled conditions.</p>
</sec>
<sec><title>Methodology/Principal Findings</title>
<p>Time-course analysis of diaphragms from lipopolysaccharide (LPS)-treated mice revealed rapid mobilization of bone marrow-derived and peritoneal macrophages to the proximity of lymphatic vessels followed by widespread (∼50%) incorporation of M-LECPs into the inflamed lymphatic vasculature. A differentiation shift toward the lymphatic phenotype was found in three LPS-induced subsets of activated macrophages that were positive for VEGFR-3 and many other lymphatic-specific markers. VEGFR-3 was strongly elevated in the early stage of macrophage transition to LECPs but undetectable in M-LECPs prior to vascular integration. Similar transient pattern of VEGFR-3 expression was found in RAW264.7 macrophages activated by LPS <italic>in vitro</italic>
. Activated RAW264.7 cells co-expressed VEGF-C that induced an autocrine signaling loop as indicated by VEGFR-3 phosphorylation inhibited by a soluble receptor. LPS-activated RAW264.7 macrophages also showed a 68% overlap with endogenous CD11b<sup>+</sup>
/VEGFR-3<sup>+</sup>
LECPs in the expression of lymphatic-specific genes. Moreover, when injected into LPS- but not saline-treated mice, GFP-tagged RAW264.7 cells massively infiltrated the inflamed diaphragm followed by integration into 18% of lymphatic vessels.</p>
</sec>
<sec><title>Conclusions/Significance</title>
<p>We present a new model for macrophage-LECP differentiation based on LPS activation of cultured RAW264.7 cells. This system designated here as the “RAW model” mimics fundamental features of endogenous M-LECPs. Unlike native LECPs, this model is unrestricted by cell numbers, heterogeneity of population, and ability to change genetic composition for experimental purposes. As such, this model can provide a valuable tool for understanding the LECP and lymphatic biology.</p>
</sec>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Shin, Ws" uniqKey="Shin W">WS Shin</name>
</author>
<author><name sortKey="Rockson, Sg" uniqKey="Rockson S">SG Rockson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Olszewski, Wl" uniqKey="Olszewski W">WL Olszewski</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tso, P" uniqKey="Tso P">P Tso</name>
</author>
<author><name sortKey="Pitts, V" uniqKey="Pitts V">V Pitts</name>
</author>
<author><name sortKey="Granger, Dn" uniqKey="Granger D">DN Granger</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Johnson, La" uniqKey="Johnson L">LA Johnson</name>
</author>
<author><name sortKey="Jackson, Dg" uniqKey="Jackson D">DG Jackson</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Mouta, C" uniqKey="Mouta C">C Mouta</name>
</author>
<author><name sortKey="Heroult, M" uniqKey="Heroult M">M Heroult</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ran, S" uniqKey="Ran S">S Ran</name>
</author>
<author><name sortKey="Volk, L" uniqKey="Volk L">L Volk</name>
</author>
<author><name sortKey="Hall, K" uniqKey="Hall K">K Hall</name>
</author>
<author><name sortKey="Flister, Mj" uniqKey="Flister M">MJ Flister</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Skobe, M" uniqKey="Skobe M">M Skobe</name>
</author>
<author><name sortKey="Hawighorst, T" uniqKey="Hawighorst T">T Hawighorst</name>
</author>
<author><name sortKey="Jackson, Dg" uniqKey="Jackson D">DG Jackson</name>
</author>
<author><name sortKey="Prevo, R" uniqKey="Prevo R">R Prevo</name>
</author>
<author><name sortKey="Janes, L" uniqKey="Janes L">L Janes</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Baluk, P" uniqKey="Baluk P">P Baluk</name>
</author>
<author><name sortKey="Tammela, T" uniqKey="Tammela T">T Tammela</name>
</author>
<author><name sortKey="Ator, E" uniqKey="Ator E">E Ator</name>
</author>
<author><name sortKey="Lyubynska, N" uniqKey="Lyubynska N">N Lyubynska</name>
</author>
<author><name sortKey="Achen, Mg" uniqKey="Achen M">MG Achen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ganta, Vc" uniqKey="Ganta V">VC Ganta</name>
</author>
<author><name sortKey="Cromer, W" uniqKey="Cromer W">W Cromer</name>
</author>
<author><name sortKey="Mills, Gl" uniqKey="Mills G">GL Mills</name>
</author>
<author><name sortKey="Traylor, J" uniqKey="Traylor J">J Traylor</name>
</author>
<author><name sortKey="Jennings, M" uniqKey="Jennings M">M Jennings</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Henno, A" uniqKey="Henno A">A Henno</name>
</author>
<author><name sortKey="Blacher, S" uniqKey="Blacher S">S Blacher</name>
</author>
<author><name sortKey="Lambert, C" uniqKey="Lambert C">C Lambert</name>
</author>
<author><name sortKey="Colige, A" uniqKey="Colige A">A Colige</name>
</author>
<author><name sortKey="Seidel, L" uniqKey="Seidel L">L Seidel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kang, S" uniqKey="Kang S">S Kang</name>
</author>
<author><name sortKey="Lee, Sp" uniqKey="Lee S">SP Lee</name>
</author>
<author><name sortKey="Kim, Ke" uniqKey="Kim K">KE Kim</name>
</author>
<author><name sortKey="Kim, Hz" uniqKey="Kim H">HZ Kim</name>
</author>
<author><name sortKey="Memet, S" uniqKey="Memet S">S Memet</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhang, Q" uniqKey="Zhang Q">Q Zhang</name>
</author>
<author><name sortKey="Lu, Y" uniqKey="Lu Y">Y Lu</name>
</author>
<author><name sortKey="Proulx, St" uniqKey="Proulx S">ST Proulx</name>
</author>
<author><name sortKey="Guo, R" uniqKey="Guo R">R Guo</name>
</author>
<author><name sortKey="Yao, Z" uniqKey="Yao Z">Z Yao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Maruyama, K" uniqKey="Maruyama K">K Maruyama</name>
</author>
<author><name sortKey="Asai, J" uniqKey="Asai J">J Asai</name>
</author>
<author><name sortKey="Ii, M" uniqKey="Ii M">M Ii</name>
</author>
<author><name sortKey="Thorne, T" uniqKey="Thorne T">T Thorne</name>
</author>
<author><name sortKey="Losordo, Dw" uniqKey="Losordo D">DW Losordo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Paavonen, K" uniqKey="Paavonen K">K Paavonen</name>
</author>
<author><name sortKey="Puolakkainen, P" uniqKey="Puolakkainen P">P Puolakkainen</name>
</author>
<author><name sortKey="Jussila, L" uniqKey="Jussila L">L Jussila</name>
</author>
<author><name sortKey="Jahkola, T" uniqKey="Jahkola T">T Jahkola</name>
</author>
<author><name sortKey="Alitalo, K" uniqKey="Alitalo K">K Alitalo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Veikkola, T" uniqKey="Veikkola T">T Veikkola</name>
</author>
<author><name sortKey="Jussila, L" uniqKey="Jussila L">L Jussila</name>
</author>
<author><name sortKey="Makinen, T" uniqKey="Makinen T">T Makinen</name>
</author>
<author><name sortKey="Karpanen, T" uniqKey="Karpanen T">T Karpanen</name>
</author>
<author><name sortKey="Jeltsch, M" uniqKey="Jeltsch M">M Jeltsch</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Makinen, T" uniqKey="Makinen T">T Makinen</name>
</author>
<author><name sortKey="Veikkola, T" uniqKey="Veikkola T">T Veikkola</name>
</author>
<author><name sortKey="Mustjoki, S" uniqKey="Mustjoki S">S Mustjoki</name>
</author>
<author><name sortKey="Karpanen, T" uniqKey="Karpanen T">T Karpanen</name>
</author>
<author><name sortKey="Catimel, B" uniqKey="Catimel B">B Catimel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Flister, Mj" uniqKey="Flister M">MJ Flister</name>
</author>
<author><name sortKey="Wilber, A" uniqKey="Wilber A">A Wilber</name>
</author>
<author><name sortKey="Hall, Kl" uniqKey="Hall K">KL Hall</name>
</author>
<author><name sortKey="Iwata, C" uniqKey="Iwata C">C Iwata</name>
</author>
<author><name sortKey="Miyazono, K" uniqKey="Miyazono K">K Miyazono</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wigle, Jt" uniqKey="Wigle J">JT Wigle</name>
</author>
<author><name sortKey="Oliver, G" uniqKey="Oliver G">G Oliver</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pytowski, B" uniqKey="Pytowski B">B Pytowski</name>
</author>
<author><name sortKey="Goldman, J" uniqKey="Goldman J">J Goldman</name>
</author>
<author><name sortKey="Persaud, K" uniqKey="Persaud K">K Persaud</name>
</author>
<author><name sortKey="Wu, Y" uniqKey="Wu Y">Y Wu</name>
</author>
<author><name sortKey="Witte, L" uniqKey="Witte L">L Witte</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Roberts, N" uniqKey="Roberts N">N Roberts</name>
</author>
<author><name sortKey="Kloos, B" uniqKey="Kloos B">B Kloos</name>
</author>
<author><name sortKey="Cassella, M" uniqKey="Cassella M">M Cassella</name>
</author>
<author><name sortKey="Podgrabinska, S" uniqKey="Podgrabinska S">S Podgrabinska</name>
</author>
<author><name sortKey="Persaud, K" uniqKey="Persaud K">K Persaud</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Achen, Mg" uniqKey="Achen M">MG Achen</name>
</author>
<author><name sortKey="Jeltsch, M" uniqKey="Jeltsch M">M Jeltsch</name>
</author>
<author><name sortKey="Kukk, E" uniqKey="Kukk E">E Kukk</name>
</author>
<author><name sortKey="Makinen, T" uniqKey="Makinen T">T Makinen</name>
</author>
<author><name sortKey="Vitali, A" uniqKey="Vitali A">A Vitali</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ristimaki, A" uniqKey="Ristimaki A">A Ristimaki</name>
</author>
<author><name sortKey="Narko, K" uniqKey="Narko K">K Narko</name>
</author>
<author><name sortKey="Enholm, B" uniqKey="Enholm B">B Enholm</name>
</author>
<author><name sortKey="Joukov, V" uniqKey="Joukov V">V Joukov</name>
</author>
<author><name sortKey="Alitalo, K" uniqKey="Alitalo K">K Alitalo</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Trompezinski, S" uniqKey="Trompezinski S">S Trompezinski</name>
</author>
<author><name sortKey="Berthier Vergnes, O" uniqKey="Berthier Vergnes O">O Berthier-Vergnes</name>
</author>
<author><name sortKey="Denis, A" uniqKey="Denis A">A Denis</name>
</author>
<author><name sortKey="Schmitt, D" uniqKey="Schmitt D">D Schmitt</name>
</author>
<author><name sortKey="Viac, J" uniqKey="Viac J">J Viac</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cursiefen, C" uniqKey="Cursiefen C">C Cursiefen</name>
</author>
<author><name sortKey="Chen, L" uniqKey="Chen L">L Chen</name>
</author>
<author><name sortKey="Borges, Lp" uniqKey="Borges L">LP Borges</name>
</author>
<author><name sortKey="Jackson, D" uniqKey="Jackson D">D Jackson</name>
</author>
<author><name sortKey="Cao, J" uniqKey="Cao J">J Cao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Iwata, C" uniqKey="Iwata C">C Iwata</name>
</author>
<author><name sortKey="Kano, Mr" uniqKey="Kano M">MR Kano</name>
</author>
<author><name sortKey="Komuro, A" uniqKey="Komuro A">A Komuro</name>
</author>
<author><name sortKey="Oka, M" uniqKey="Oka M">M Oka</name>
</author>
<author><name sortKey="Kiyono, K" uniqKey="Kiyono K">K Kiyono</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Srinivasan, Rs" uniqKey="Srinivasan R">RS Srinivasan</name>
</author>
<author><name sortKey="Dillard, Me" uniqKey="Dillard M">ME Dillard</name>
</author>
<author><name sortKey="Lagutin, Ov" uniqKey="Lagutin O">OV Lagutin</name>
</author>
<author><name sortKey="Lin, Fj" uniqKey="Lin F">FJ Lin</name>
</author>
<author><name sortKey="Tsai, S" uniqKey="Tsai S">S Tsai</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jiang, S" uniqKey="Jiang S">S Jiang</name>
</author>
<author><name sortKey="Bailey, As" uniqKey="Bailey A">AS Bailey</name>
</author>
<author><name sortKey="Goldman, Dc" uniqKey="Goldman D">DC Goldman</name>
</author>
<author><name sortKey="Swain, Jr" uniqKey="Swain J">JR Swain</name>
</author>
<author><name sortKey="Wong, Mh" uniqKey="Wong M">MH Wong</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zumsteg, A" uniqKey="Zumsteg A">A Zumsteg</name>
</author>
<author><name sortKey="Baeriswyl, V" uniqKey="Baeriswyl V">V Baeriswyl</name>
</author>
<author><name sortKey="Imaizumi, N" uniqKey="Imaizumi N">N Imaizumi</name>
</author>
<author><name sortKey="Schwendener, R" uniqKey="Schwendener R">R Schwendener</name>
</author>
<author><name sortKey="Ruegg, C" uniqKey="Ruegg C">C Ruegg</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kerjaschki, D" uniqKey="Kerjaschki D">D Kerjaschki</name>
</author>
<author><name sortKey="Huttary, N" uniqKey="Huttary N">N Huttary</name>
</author>
<author><name sortKey="Raab, I" uniqKey="Raab I">I Raab</name>
</author>
<author><name sortKey="Regele, H" uniqKey="Regele H">H Regele</name>
</author>
<author><name sortKey="Bojarski Nagy, K" uniqKey="Bojarski Nagy K">K Bojarski-Nagy</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Religa, P" uniqKey="Religa P">P Religa</name>
</author>
<author><name sortKey="Cao, R" uniqKey="Cao R">R Cao</name>
</author>
<author><name sortKey="Bjorndahl, M" uniqKey="Bjorndahl M">M Bjorndahl</name>
</author>
<author><name sortKey="Zhou, Z" uniqKey="Zhou Z">Z Zhou</name>
</author>
<author><name sortKey="Zhu, Z" uniqKey="Zhu Z">Z Zhu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lee, Jy" uniqKey="Lee J">JY Lee</name>
</author>
<author><name sortKey="Park, C" uniqKey="Park C">C Park</name>
</author>
<author><name sortKey="Cho, Yp" uniqKey="Cho Y">YP Cho</name>
</author>
<author><name sortKey="Lee, E" uniqKey="Lee E">E Lee</name>
</author>
<author><name sortKey="Kim, H" uniqKey="Kim H">H Kim</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Buttler, K" uniqKey="Buttler K">K Buttler</name>
</author>
<author><name sortKey="Ezaki, T" uniqKey="Ezaki T">T Ezaki</name>
</author>
<author><name sortKey="Wilting, J" uniqKey="Wilting J">J Wilting</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Maruyama, K" uniqKey="Maruyama K">K Maruyama</name>
</author>
<author><name sortKey="Ii, M" uniqKey="Ii M">M Ii</name>
</author>
<author><name sortKey="Cursiefen, C" uniqKey="Cursiefen C">C Cursiefen</name>
</author>
<author><name sortKey="Jackson, Dg" uniqKey="Jackson D">DG Jackson</name>
</author>
<author><name sortKey="Keino, H" uniqKey="Keino H">H Keino</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Suzuki, H" uniqKey="Suzuki H">H Suzuki</name>
</author>
<author><name sortKey="Watabe, T" uniqKey="Watabe T">T Watabe</name>
</author>
<author><name sortKey="Kato, M" uniqKey="Kato M">M Kato</name>
</author>
<author><name sortKey="Miyazawa, K" uniqKey="Miyazawa K">K Miyazawa</name>
</author>
<author><name sortKey="Miyazono, K" uniqKey="Miyazono K">K Miyazono</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Conrad, C" uniqKey="Conrad C">C Conrad</name>
</author>
<author><name sortKey="Niess, H" uniqKey="Niess H">H Niess</name>
</author>
<author><name sortKey="Huss, R" uniqKey="Huss R">R Huss</name>
</author>
<author><name sortKey="Huber, S" uniqKey="Huber S">S Huber</name>
</author>
<author><name sortKey="Von Luettichau, I" uniqKey="Von Luettichau I">I von Luettichau</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Cimato, T" uniqKey="Cimato T">T Cimato</name>
</author>
<author><name sortKey="Beers, J" uniqKey="Beers J">J Beers</name>
</author>
<author><name sortKey="Ding, S" uniqKey="Ding S">S Ding</name>
</author>
<author><name sortKey="Ma, M" uniqKey="Ma M">M Ma</name>
</author>
<author><name sortKey="Mccoy, Jp" uniqKey="Mccoy J">JP McCoy</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Skobe, M" uniqKey="Skobe M">M Skobe</name>
</author>
<author><name sortKey="Hamberg, Lm" uniqKey="Hamberg L">LM Hamberg</name>
</author>
<author><name sortKey="Hawighorst, T" uniqKey="Hawighorst T">T Hawighorst</name>
</author>
<author><name sortKey="Schirner, M" uniqKey="Schirner M">M Schirner</name>
</author>
<author><name sortKey="Wolf, Gl" uniqKey="Wolf G">GL Wolf</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Saaristo, A" uniqKey="Saaristo A">A Saaristo</name>
</author>
<author><name sortKey="Tammela, T" uniqKey="Tammela T">T Tammela</name>
</author>
<author><name sortKey="Farkkila, A" uniqKey="Farkkila A">A Farkkila</name>
</author>
<author><name sortKey="Karkkainen, M" uniqKey="Karkkainen M">M Karkkainen</name>
</author>
<author><name sortKey="Suominen, E" uniqKey="Suominen E">E Suominen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kim, Ke" uniqKey="Kim K">KE Kim</name>
</author>
<author><name sortKey="Koh, Yj" uniqKey="Koh Y">YJ Koh</name>
</author>
<author><name sortKey="Jeon, Bh" uniqKey="Jeon B">BH Jeon</name>
</author>
<author><name sortKey="Jang, C" uniqKey="Jang C">C Jang</name>
</author>
<author><name sortKey="Han, J" uniqKey="Han J">J Han</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Young, Pp" uniqKey="Young P">PP Young</name>
</author>
<author><name sortKey="Ardestani, S" uniqKey="Ardestani S">S Ardestani</name>
</author>
<author><name sortKey="Li, B" uniqKey="Li B">B Li</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gordon, S" uniqKey="Gordon S">S Gordon</name>
</author>
<author><name sortKey="Taylor, Pr" uniqKey="Taylor P">PR Taylor</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ralph, P" uniqKey="Ralph P">P Ralph</name>
</author>
<author><name sortKey="Nakoinz, I" uniqKey="Nakoinz I">I Nakoinz</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Flister, Mj" uniqKey="Flister M">MJ Flister</name>
</author>
<author><name sortKey="Volk, Ld" uniqKey="Volk L">LD Volk</name>
</author>
<author><name sortKey="Ran, S" uniqKey="Ran S">S Ran</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jeon, Bh" uniqKey="Jeon B">BH Jeon</name>
</author>
<author><name sortKey="Jang, C" uniqKey="Jang C">C Jang</name>
</author>
<author><name sortKey="Han, J" uniqKey="Han J">J Han</name>
</author>
<author><name sortKey="Kataru, Rp" uniqKey="Kataru R">RP Kataru</name>
</author>
<author><name sortKey="Piao, L" uniqKey="Piao L">L Piao</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Watari, K" uniqKey="Watari K">K Watari</name>
</author>
<author><name sortKey="Nakao, S" uniqKey="Nakao S">S Nakao</name>
</author>
<author><name sortKey="Fotovati, A" uniqKey="Fotovati A">A Fotovati</name>
</author>
<author><name sortKey="Basaki, Y" uniqKey="Basaki Y">Y Basaki</name>
</author>
<author><name sortKey="Hosoi, F" uniqKey="Hosoi F">F Hosoi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Makinen, T" uniqKey="Makinen T">T Makinen</name>
</author>
<author><name sortKey="Jussila, L" uniqKey="Jussila L">L Jussila</name>
</author>
<author><name sortKey="Veikkola, T" uniqKey="Veikkola T">T Veikkola</name>
</author>
<author><name sortKey="Karpanen, T" uniqKey="Karpanen T">T Karpanen</name>
</author>
<author><name sortKey="Kettunen, Mi" uniqKey="Kettunen M">MI Kettunen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Salven, P" uniqKey="Salven P">P Salven</name>
</author>
<author><name sortKey="Mustjoki, S" uniqKey="Mustjoki S">S Mustjoki</name>
</author>
<author><name sortKey="Alitalo, R" uniqKey="Alitalo R">R Alitalo</name>
</author>
<author><name sortKey="Alitalo, K" uniqKey="Alitalo K">K Alitalo</name>
</author>
<author><name sortKey="Rafii, S" uniqKey="Rafii S">S Rafii</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Bogos, K" uniqKey="Bogos K">K Bogos</name>
</author>
<author><name sortKey="Renyi Vamos, F" uniqKey="Renyi Vamos F">F Renyi-Vamos</name>
</author>
<author><name sortKey="Dobos, J" uniqKey="Dobos J">J Dobos</name>
</author>
<author><name sortKey="Kenessey, I" uniqKey="Kenessey I">I Kenessey</name>
</author>
<author><name sortKey="Tovari, J" uniqKey="Tovari J">J Tovari</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hosking, B" uniqKey="Hosking B">B Hosking</name>
</author>
<author><name sortKey="Francois, M" uniqKey="Francois M">M Francois</name>
</author>
<author><name sortKey="Wilhelm, D" uniqKey="Wilhelm D">D Wilhelm</name>
</author>
<author><name sortKey="Orsenigo, F" uniqKey="Orsenigo F">F Orsenigo</name>
</author>
<author><name sortKey="Caprini, A" uniqKey="Caprini A">A Caprini</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Francois, M" uniqKey="Francois M">M Francois</name>
</author>
<author><name sortKey="Caprini, A" uniqKey="Caprini A">A Caprini</name>
</author>
<author><name sortKey="Hosking, B" uniqKey="Hosking B">B Hosking</name>
</author>
<author><name sortKey="Orsenigo, F" uniqKey="Orsenigo F">F Orsenigo</name>
</author>
<author><name sortKey="Wilhelm, D" uniqKey="Wilhelm D">D Wilhelm</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Shawber, Cj" uniqKey="Shawber C">CJ Shawber</name>
</author>
<author><name sortKey="Funahashi, Y" uniqKey="Funahashi Y">Y Funahashi</name>
</author>
<author><name sortKey="Francisco, E" uniqKey="Francisco E">E Francisco</name>
</author>
<author><name sortKey="Vorontchikhina, M" uniqKey="Vorontchikhina M">M Vorontchikhina</name>
</author>
<author><name sortKey="Kitamura, Y" uniqKey="Kitamura Y">Y Kitamura</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Srinivasan, Rs" uniqKey="Srinivasan R">RS Srinivasan</name>
</author>
<author><name sortKey="Geng, X" uniqKey="Geng X">X Geng</name>
</author>
<author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name>
</author>
<author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name>
</author>
<author><name sortKey="Mukatira, S" uniqKey="Mukatira S">S Mukatira</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lin, Fj" uniqKey="Lin F">FJ Lin</name>
</author>
<author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name>
</author>
<author><name sortKey="Qin, J" uniqKey="Qin J">J Qin</name>
</author>
<author><name sortKey="Hong, Yk" uniqKey="Hong Y">YK Hong</name>
</author>
<author><name sortKey="Tsai, Mj" uniqKey="Tsai M">MJ Tsai</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Banerji, S" uniqKey="Banerji S">S Banerji</name>
</author>
<author><name sortKey="Ni, J" uniqKey="Ni J">J Ni</name>
</author>
<author><name sortKey="Wang, Sx" uniqKey="Wang S">SX Wang</name>
</author>
<author><name sortKey="Clasper, S" uniqKey="Clasper S">S Clasper</name>
</author>
<author><name sortKey="Su, J" uniqKey="Su J">J Su</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Schacht, V" uniqKey="Schacht V">V Schacht</name>
</author>
<author><name sortKey="Ramirez, Mi" uniqKey="Ramirez M">MI Ramirez</name>
</author>
<author><name sortKey="Hong, Yk" uniqKey="Hong Y">YK Hong</name>
</author>
<author><name sortKey="Hirakawa, S" uniqKey="Hirakawa S">S Hirakawa</name>
</author>
<author><name sortKey="Feng, D" uniqKey="Feng D">D Feng</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Vlahakis, Ne" uniqKey="Vlahakis N">NE Vlahakis</name>
</author>
<author><name sortKey="Young, Ba" uniqKey="Young B">BA Young</name>
</author>
<author><name sortKey="Atakilit, A" uniqKey="Atakilit A">A Atakilit</name>
</author>
<author><name sortKey="Sheppard, D" uniqKey="Sheppard D">D Sheppard</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="De Palma, M" uniqKey="De Palma M">M De Palma</name>
</author>
<author><name sortKey="Venneri, Ma" uniqKey="Venneri M">MA Venneri</name>
</author>
<author><name sortKey="Galli, R" uniqKey="Galli R">R Galli</name>
</author>
<author><name sortKey="Sergi, Sl" uniqKey="Sergi S">SL Sergi</name>
</author>
<author><name sortKey="Politi, Ls" uniqKey="Politi L">LS Politi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Coffelt, Sb" uniqKey="Coffelt S">SB Coffelt</name>
</author>
<author><name sortKey="Tal, Ao" uniqKey="Tal A">AO Tal</name>
</author>
<author><name sortKey="Scholz, A" uniqKey="Scholz A">A Scholz</name>
</author>
<author><name sortKey="De Palma, M" uniqKey="De Palma M">M De Palma</name>
</author>
<author><name sortKey="Patel, S" uniqKey="Patel S">S Patel</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Pucci, F" uniqKey="Pucci F">F Pucci</name>
</author>
<author><name sortKey="Venneri, Ma" uniqKey="Venneri M">MA Venneri</name>
</author>
<author><name sortKey="Biziato, D" uniqKey="Biziato D">D Biziato</name>
</author>
<author><name sortKey="Nonis, A" uniqKey="Nonis A">A Nonis</name>
</author>
<author><name sortKey="Moi, D" uniqKey="Moi D">D Moi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Klagsbrun, M" uniqKey="Klagsbrun M">M Klagsbrun</name>
</author>
<author><name sortKey="Eichmann, A" uniqKey="Eichmann A">A Eichmann</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Kono, T" uniqKey="Kono T">T Kono</name>
</author>
<author><name sortKey="Kubo, H" uniqKey="Kubo H">H Kubo</name>
</author>
<author><name sortKey="Shimazu, C" uniqKey="Shimazu C">C Shimazu</name>
</author>
<author><name sortKey="Ueda, Y" uniqKey="Ueda Y">Y Ueda</name>
</author>
<author><name sortKey="Takahashi, M" uniqKey="Takahashi M">M Takahashi</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hartley, Jw" uniqKey="Hartley J">JW Hartley</name>
</author>
<author><name sortKey="Evans, Lh" uniqKey="Evans L">LH Evans</name>
</author>
<author><name sortKey="Green, Ky" uniqKey="Green K">KY Green</name>
</author>
<author><name sortKey="Naghashfar, Z" uniqKey="Naghashfar Z">Z Naghashfar</name>
</author>
<author><name sortKey="Macias, Ar" uniqKey="Macias A">AR Macias</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Natarajan, M" uniqKey="Natarajan M">M Natarajan</name>
</author>
<author><name sortKey="Lin, Km" uniqKey="Lin K">KM Lin</name>
</author>
<author><name sortKey="Hsueh, Rc" uniqKey="Hsueh R">RC Hsueh</name>
</author>
<author><name sortKey="Sternweis, Pc" uniqKey="Sternweis P">PC Sternweis</name>
</author>
<author><name sortKey="Ranganathan, R" uniqKey="Ranganathan R">R Ranganathan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Schmittgen, Td" uniqKey="Schmittgen T">TD Schmittgen</name>
</author>
<author><name sortKey="Livak, Kj" uniqKey="Livak K">KJ Livak</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title-group><journal-title>PLoS ONE</journal-title>
</journal-title-group>
<issn pub-type="epub">1932-6203</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22396739</article-id>
<article-id pub-id-type="pmc">3292559</article-id>
<article-id pub-id-type="publisher-id">PONE-D-11-08981</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0031794</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v2"><subject>Biology</subject>
<subj-group><subject>Developmental Biology</subject>
<subj-group><subject>Molecular Development</subject>
</subj-group>
<subj-group><subject>Stem Cells</subject>
</subj-group>
</subj-group>
<subj-group><subject>Immunology</subject>
<subj-group><subject>Immune Cells</subject>
</subj-group>
<subj-group><subject>Immune System</subject>
</subj-group>
<subj-group><subject>Immunity</subject>
</subj-group>
</subj-group>
<subj-group><subject>Molecular Cell Biology</subject>
<subj-group><subject>Cellular Types</subject>
</subj-group>
<subj-group><subject>Signal Transduction</subject>
<subj-group><subject>Signaling in Cellular Processes</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>New Model of Macrophage Acquisition of the Lymphatic Endothelial Phenotype</article-title>
<alt-title alt-title-type="running-head">Macrophage Differentiation to Lymphatic Phenotype</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Hall</surname>
<given-names>Kelly L.</given-names>
</name>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Volk-Draper</surname>
<given-names>Lisa D.</given-names>
</name>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Flister</surname>
<given-names>Michael J.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Ran</surname>
<given-names>Sophia</given-names>
</name>
<xref ref-type="aff" rid="aff1"></xref>
<xref ref-type="corresp" rid="cor1"><sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="aff1"><addr-line>Department of Medical Microbiology, Immunology, and Cell Biology, Southern Illinois University School of Medicine, Springfield, Illinois, United States of America</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Bonecchi</surname>
<given-names>Raffaella</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1">Università degli Studi di Milano, Italy</aff>
<author-notes><corresp id="cor1">* E-mail: <email>sran@siumed.edu</email>
</corresp>
<fn fn-type="con"><p>Conceived and designed the experiments: SR. Performed the experiments: KLH LDV MJF. Analyzed the data: MJF KLH LDV SR. Wrote the paper: SR MJF.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2012</year>
</pub-date>
<pub-date pub-type="epub"><day>2</day>
<month>3</month>
<year>2012</year>
</pub-date>
<volume>7</volume>
<issue>3</issue>
<elocation-id>e31794</elocation-id>
<history><date date-type="received"><day>18</day>
<month>5</month>
<year>2011</year>
</date>
<date date-type="accepted"><day>19</day>
<month>1</month>
<year>2012</year>
</date>
</history>
<permissions><copyright-statement>Hall et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</copyright-statement>
<copyright-year>2012</copyright-year>
</permissions>
<abstract><sec><title>Background</title>
<p>Macrophage-derived lymphatic endothelial cell progenitors (M-LECPs) contribute to new lymphatic vessel formation, but the mechanisms regulating their differentiation, recruitment, and function are poorly understood. Detailed characterization of M-LECPs is limited by low frequency <italic>in vivo</italic>
and lack of model systems allowing in-depth molecular analyses <italic>in vitro</italic>
. Our goal was to establish a cell culture model to characterize inflammation-induced macrophage-to-LECP differentiation under controlled conditions.</p>
</sec>
<sec><title>Methodology/Principal Findings</title>
<p>Time-course analysis of diaphragms from lipopolysaccharide (LPS)-treated mice revealed rapid mobilization of bone marrow-derived and peritoneal macrophages to the proximity of lymphatic vessels followed by widespread (∼50%) incorporation of M-LECPs into the inflamed lymphatic vasculature. A differentiation shift toward the lymphatic phenotype was found in three LPS-induced subsets of activated macrophages that were positive for VEGFR-3 and many other lymphatic-specific markers. VEGFR-3 was strongly elevated in the early stage of macrophage transition to LECPs but undetectable in M-LECPs prior to vascular integration. Similar transient pattern of VEGFR-3 expression was found in RAW264.7 macrophages activated by LPS <italic>in vitro</italic>
. Activated RAW264.7 cells co-expressed VEGF-C that induced an autocrine signaling loop as indicated by VEGFR-3 phosphorylation inhibited by a soluble receptor. LPS-activated RAW264.7 macrophages also showed a 68% overlap with endogenous CD11b<sup>+</sup>
/VEGFR-3<sup>+</sup>
LECPs in the expression of lymphatic-specific genes. Moreover, when injected into LPS- but not saline-treated mice, GFP-tagged RAW264.7 cells massively infiltrated the inflamed diaphragm followed by integration into 18% of lymphatic vessels.</p>
</sec>
<sec><title>Conclusions/Significance</title>
<p>We present a new model for macrophage-LECP differentiation based on LPS activation of cultured RAW264.7 cells. This system designated here as the “RAW model” mimics fundamental features of endogenous M-LECPs. Unlike native LECPs, this model is unrestricted by cell numbers, heterogeneity of population, and ability to change genetic composition for experimental purposes. As such, this model can provide a valuable tool for understanding the LECP and lymphatic biology.</p>
</sec>
</abstract>
<counts><page-count count="1"></page-count>
</counts>
</article-meta>
</front>
</pmc>
<affiliations><list></list>
<tree><noCountry><name sortKey="Flister, Michael J" sort="Flister, Michael J" uniqKey="Flister M" first="Michael J." last="Flister">Michael J. Flister</name>
<name sortKey="Hall, Kelly L" sort="Hall, Kelly L" uniqKey="Hall K" first="Kelly L." last="Hall">Kelly L. Hall</name>
<name sortKey="Ran, Sophia" sort="Ran, Sophia" uniqKey="Ran S" first="Sophia" last="Ran">Sophia Ran</name>
<name sortKey="Volk Draper, Lisa D" sort="Volk Draper, Lisa D" uniqKey="Volk Draper L" first="Lisa D." last="Volk-Draper">Lisa D. Volk-Draper</name>
</noCountry>
</tree>
</affiliations>
</record>
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