Human Podoplanin-positive Monocytes and Platelets Enhance Lymphangiogenesis Through the Activation of the Podoplanin/CLEC-2 Axis
Identifieur interne : 006576 ( Ncbi/Curation ); précédent : 006575; suivant : 006577Human Podoplanin-positive Monocytes and Platelets Enhance Lymphangiogenesis Through the Activation of the Podoplanin/CLEC-2 Axis
Auteurs : Jin Hur [Corée du Sud] ; Jae Hee Jang [Corée du Sud] ; Il-Young Oh [Corée du Sud] ; Jae-Il Choi [Corée du Sud] ; Ji-Yeon Yun [Corée du Sud] ; Joonoh Kim [Corée du Sud] ; Young-Eun Choi [Corée du Sud] ; Seung-Bum Ko [Corée du Sud] ; Jin-A Kang [Corée du Sud] ; Jeehoon Kang [Corée du Sud] ; Sang Eun Lee [Corée du Sud] ; Hwan Lee [Corée du Sud] ; Young-Bae Park [Corée du Sud] ; Hyo-Soo Kim [Corée du Sud]Source :
- Molecular Therapy [ 1525-0016 ] ; 2014.
Abstract
Emerging studies suggested that murine podoplanin-positive monocytes (PPMs) are involved in lymphangiogenesis. The goal of this study was to demonstrate the therapeutic lymphangiogenesis of human PPMs by the interaction with platelets. Aggregation culture of human peripheral blood mononuclear cells (PBMCs) resulted in cellular aggregates termed hematospheres. During 5-day culture, PPMs expanded exponentially and expressed several lymphatic endothelial cell–specific markers including vascular endothelial growth factor receptor (VEGFR)-3 and well-established lymphangiogenic transcription factors. Next, we investigated the potential interaction of PPMs with platelets that had C-type lectin–like receptor-2 (CLEC-2), a receptor of podoplanin.
Url:
DOI: 10.1038/mt.2014.61
PubMed: 24736277
PubMed Central: 4435587
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Human Podoplanin-positive Monocytes and Platelets Enhance Lymphangiogenesis Through the Activation of the Podoplanin/CLEC-2 Axis</title>
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<author><name sortKey="Jang, Jae Hee" sort="Jang, Jae Hee" uniqKey="Jang J" first="Jae Hee" last="Jang">Jae Hee Jang</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</nlm:aff>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Kang, Jeehoon" sort="Kang, Jeehoon" uniqKey="Kang J" first="Jeehoon" last="Kang">Jeehoon Kang</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</nlm:aff>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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<author><name sortKey="Lee, Sang Eun" sort="Lee, Sang Eun" uniqKey="Lee S" first="Sang Eun" last="Lee">Sang Eun Lee</name>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</nlm:aff>
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<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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, Seoul,<country>Republic of Korea</country>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Park, Young Bae" sort="Park, Young Bae" uniqKey="Park Y" first="Young-Bae" last="Park">Young-Bae Park</name>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Innovative Research Institute for Cell Therapy, Seoul National University Hospital</institution>
, Seoul,<country>Republic of Korea</country>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kim, Hyo Soo" sort="Kim, Hyo Soo" uniqKey="Kim H" first="Hyo-Soo" last="Kim">Hyo-Soo Kim</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution>National Research Laboratory for Stem Cell Niche, Seoul National University Hospital</institution>
, Seoul,<country>Republic of Korea</country>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Innovative Research Institute for Cell Therapy, Seoul National University Hospital</institution>
, Seoul,<country>Republic of Korea</country>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University Hospital</institution>
, Seoul,<country>Republic of Korea</country>
</nlm:aff>
<country xml:lang="fr">Corée du Sud</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">Molecular Therapy</title>
<idno type="ISSN">1525-0016</idno>
<idno type="eISSN">1525-0024</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>Emerging studies suggested that murine podoplanin-positive monocytes (PPMs) are involved in lymphangiogenesis. The goal of this study was to demonstrate the therapeutic lymphangiogenesis of human PPMs by the interaction with platelets. Aggregation culture of human peripheral blood mononuclear cells (PBMCs) resulted in cellular aggregates termed hematospheres. During 5-day culture, PPMs expanded exponentially and expressed several lymphatic endothelial cell–specific markers including vascular endothelial growth factor receptor (VEGFR)-3 and well-established lymphangiogenic transcription factors. Next, we investigated the potential interaction of PPMs with platelets that had C-type lectin–like receptor-2 (CLEC-2), a receptor of podoplanin. <italic>In vitro</italic>
coculture of PPMs and platelets stimulated PPMs to strongly express lymphatic endothelial markers and upregulate lymphangiogenic cytokines. Recombinant human CLEC-2 also stimulated PPMs through Akt and Erk signaling. Likewise, platelets in coculture with PPMs augmented secretion of a lymphangiogenic cytokine, interleukin (IL)-1-β, via podoplanin/CLEC-2 axis. The supernatant obtained from coculture was able to enhance the migration, viability, and proliferation of lymphatic endothelial cell. Local injection of hematospheres with platelets significantly increased lymphatic neovascularization and facilitated wound healing in the full-thickness skin wounds of nude mice. Cotreatment with PPMs and platelets augments lymphangiogenesis through podoplanin/CLEC-2 axis, which thus would be a promising novel strategy of cell therapy to treat human lymphatic vessel disease.</p>
</div>
</front>
</TEI>
</record>
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