Lymphatic endothelial-cell expressed ACKR3 is dispensable for postnatal lymphangiogenesis and lymphatic drainage function in mice.
Atypical chemokine receptor ACKR3 (formerly CXCR7) is a scavenging receptor that has recently been implicated in murine lymphatic development. Specifically, ACKR3-deficiency was shown to result in lymphatic hyperplasia and lymphedema, in addition to cardiac hyperplasia and cardiac valve defects lead...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0249068 |
| _version_ | 1818928644853071872 |
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| author | Elena C Sigmund Lilian Baur Philipp Schineis Jorge Arasa Victor Collado-Diaz Martina Vranova Rolf A K Stahl Marcus Thelen Cornelia Halin |
| author_facet | Elena C Sigmund Lilian Baur Philipp Schineis Jorge Arasa Victor Collado-Diaz Martina Vranova Rolf A K Stahl Marcus Thelen Cornelia Halin |
| author_sort | Elena C Sigmund |
| collection | DOAJ |
| description | Atypical chemokine receptor ACKR3 (formerly CXCR7) is a scavenging receptor that has recently been implicated in murine lymphatic development. Specifically, ACKR3-deficiency was shown to result in lymphatic hyperplasia and lymphedema, in addition to cardiac hyperplasia and cardiac valve defects leading to embryonic lethality. The lymphatic phenotype was attributed to a lymphatic endothelial cell (LEC)-intrinsic scavenging function of ACKR3 for the vascular peptide hormone adrenomedullin (AM), which is also important during postnatal lymphangiogenesis. In this study, we investigated the expression of ACKR3 in the lymphatic vasculature of adult mice and its function in postnatal lymphatic development and function. We show that ACKR3 is widely expressed in mature lymphatics and that it exerts chemokine-scavenging activity in cultured murine skin-derived LECs. To investigate the role of LEC-expressed ACKR3 in postnatal lymphangiogenesis and function during adulthood, we generated and validated a lymphatic-specific, inducible ACKR3 knockout mouse. Surprisingly, in contrast to the reported involvement of ACKR3 in lymphatic development, our analyses revealed no contribution of LEC-expressed ACKR3 to postnatal lymphangiogenesis, lymphatic morphology and drainage function. |
| first_indexed | 2024-12-20T03:32:11Z |
| format | Article |
| id | doaj.art-00cb1bafafed433f9389a983fb5f9f10 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T03:32:11Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-00cb1bafafed433f9389a983fb5f9f102022-12-21T19:54:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01164e024906810.1371/journal.pone.0249068Lymphatic endothelial-cell expressed ACKR3 is dispensable for postnatal lymphangiogenesis and lymphatic drainage function in mice.Elena C SigmundLilian BaurPhilipp SchineisJorge ArasaVictor Collado-DiazMartina VranovaRolf A K StahlMarcus ThelenCornelia HalinAtypical chemokine receptor ACKR3 (formerly CXCR7) is a scavenging receptor that has recently been implicated in murine lymphatic development. Specifically, ACKR3-deficiency was shown to result in lymphatic hyperplasia and lymphedema, in addition to cardiac hyperplasia and cardiac valve defects leading to embryonic lethality. The lymphatic phenotype was attributed to a lymphatic endothelial cell (LEC)-intrinsic scavenging function of ACKR3 for the vascular peptide hormone adrenomedullin (AM), which is also important during postnatal lymphangiogenesis. In this study, we investigated the expression of ACKR3 in the lymphatic vasculature of adult mice and its function in postnatal lymphatic development and function. We show that ACKR3 is widely expressed in mature lymphatics and that it exerts chemokine-scavenging activity in cultured murine skin-derived LECs. To investigate the role of LEC-expressed ACKR3 in postnatal lymphangiogenesis and function during adulthood, we generated and validated a lymphatic-specific, inducible ACKR3 knockout mouse. Surprisingly, in contrast to the reported involvement of ACKR3 in lymphatic development, our analyses revealed no contribution of LEC-expressed ACKR3 to postnatal lymphangiogenesis, lymphatic morphology and drainage function.https://doi.org/10.1371/journal.pone.0249068 |
| spellingShingle | Elena C Sigmund Lilian Baur Philipp Schineis Jorge Arasa Victor Collado-Diaz Martina Vranova Rolf A K Stahl Marcus Thelen Cornelia Halin Lymphatic endothelial-cell expressed ACKR3 is dispensable for postnatal lymphangiogenesis and lymphatic drainage function in mice. PLoS ONE |
| title | Lymphatic endothelial-cell expressed ACKR3 is dispensable for postnatal lymphangiogenesis and lymphatic drainage function in mice. |
| title_full | Lymphatic endothelial-cell expressed ACKR3 is dispensable for postnatal lymphangiogenesis and lymphatic drainage function in mice. |
| title_fullStr | Lymphatic endothelial-cell expressed ACKR3 is dispensable for postnatal lymphangiogenesis and lymphatic drainage function in mice. |
| title_full_unstemmed | Lymphatic endothelial-cell expressed ACKR3 is dispensable for postnatal lymphangiogenesis and lymphatic drainage function in mice. |
| title_short | Lymphatic endothelial-cell expressed ACKR3 is dispensable for postnatal lymphangiogenesis and lymphatic drainage function in mice. |
| title_sort | lymphatic endothelial cell expressed ackr3 is dispensable for postnatal lymphangiogenesis and lymphatic drainage function in mice |
| url | https://doi.org/10.1371/journal.pone.0249068 |
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