Hematopoietic sphingosine 1-phosphate lyase deficiency decreases atherosclerotic lesion development in LDL-receptor deficient mice.
Altered sphingosine 1-phosphate (S1P) homeostasis and signaling is implicated in various inflammatory diseases including atherosclerosis. As S1P levels are tightly controlled by S1P lyase, we investigated the impact of hematopoietic S1P lyase (Sgpl1(-/-)) deficiency on leukocyte subsets relevant to...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3659045?pdf=render |
| _version_ | 1818133709304365056 |
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| author | Martine Bot Paul P Van Veldhoven Saskia C A de Jager Jason Johnson Niels Nijstad Peter J Van Santbrink Marijke M Westra Gerd Van Der Hoeven Marion J Gijbels Carsten Müller-Tidow Georg Varga Uwe J F Tietge Johan Kuiper Theo J C Van Berkel Jerzy-Roch Nofer Ilze Bot Erik A L Biessen |
| author_facet | Martine Bot Paul P Van Veldhoven Saskia C A de Jager Jason Johnson Niels Nijstad Peter J Van Santbrink Marijke M Westra Gerd Van Der Hoeven Marion J Gijbels Carsten Müller-Tidow Georg Varga Uwe J F Tietge Johan Kuiper Theo J C Van Berkel Jerzy-Roch Nofer Ilze Bot Erik A L Biessen |
| author_sort | Martine Bot |
| collection | DOAJ |
| description | Altered sphingosine 1-phosphate (S1P) homeostasis and signaling is implicated in various inflammatory diseases including atherosclerosis. As S1P levels are tightly controlled by S1P lyase, we investigated the impact of hematopoietic S1P lyase (Sgpl1(-/-)) deficiency on leukocyte subsets relevant to atherosclerosis.LDL receptor deficient mice that were transplanted with Sgpl1(-/-) bone marrow showed disrupted S1P gradients translating into lymphopenia and abrogated lymphocyte mitogenic and cytokine response as compared to controls. Remarkably however, Sgpl1(-/-) chimeras displayed mild monocytosis, due to impeded stromal retention and myelopoiesis, and plasma cytokine and macrophage expression patterns, that were largely compatible with classical macrophage activation. Collectively these two phenotypic features of Sgpl1 deficiency culminated in diminished atherogenic response.Here we not only firmly establish the critical role of hematopoietic S1P lyase in controlling S1P levels and T cell trafficking in blood and lymphoid tissue, but also identify leukocyte Sgpl1 as critical factor in monocyte macrophage differentiation and function. Its, partly counterbalancing, pro- and anti-inflammatory activity spectrum imply that intervention in S1P lyase function in inflammatory disorders such as atherosclerosis should be considered with caution. |
| first_indexed | 2024-12-11T08:57:02Z |
| format | Article |
| id | doaj.art-1a0d95655b81411ea2e0c24d8f384462 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T08:57:02Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1a0d95655b81411ea2e0c24d8f3844622022-12-22T01:13:52ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6336010.1371/journal.pone.0063360Hematopoietic sphingosine 1-phosphate lyase deficiency decreases atherosclerotic lesion development in LDL-receptor deficient mice.Martine BotPaul P Van VeldhovenSaskia C A de JagerJason JohnsonNiels NijstadPeter J Van SantbrinkMarijke M WestraGerd Van Der HoevenMarion J GijbelsCarsten Müller-TidowGeorg VargaUwe J F TietgeJohan KuiperTheo J C Van BerkelJerzy-Roch NoferIlze BotErik A L BiessenAltered sphingosine 1-phosphate (S1P) homeostasis and signaling is implicated in various inflammatory diseases including atherosclerosis. As S1P levels are tightly controlled by S1P lyase, we investigated the impact of hematopoietic S1P lyase (Sgpl1(-/-)) deficiency on leukocyte subsets relevant to atherosclerosis.LDL receptor deficient mice that were transplanted with Sgpl1(-/-) bone marrow showed disrupted S1P gradients translating into lymphopenia and abrogated lymphocyte mitogenic and cytokine response as compared to controls. Remarkably however, Sgpl1(-/-) chimeras displayed mild monocytosis, due to impeded stromal retention and myelopoiesis, and plasma cytokine and macrophage expression patterns, that were largely compatible with classical macrophage activation. Collectively these two phenotypic features of Sgpl1 deficiency culminated in diminished atherogenic response.Here we not only firmly establish the critical role of hematopoietic S1P lyase in controlling S1P levels and T cell trafficking in blood and lymphoid tissue, but also identify leukocyte Sgpl1 as critical factor in monocyte macrophage differentiation and function. Its, partly counterbalancing, pro- and anti-inflammatory activity spectrum imply that intervention in S1P lyase function in inflammatory disorders such as atherosclerosis should be considered with caution.http://europepmc.org/articles/PMC3659045?pdf=render |
| spellingShingle | Martine Bot Paul P Van Veldhoven Saskia C A de Jager Jason Johnson Niels Nijstad Peter J Van Santbrink Marijke M Westra Gerd Van Der Hoeven Marion J Gijbels Carsten Müller-Tidow Georg Varga Uwe J F Tietge Johan Kuiper Theo J C Van Berkel Jerzy-Roch Nofer Ilze Bot Erik A L Biessen Hematopoietic sphingosine 1-phosphate lyase deficiency decreases atherosclerotic lesion development in LDL-receptor deficient mice. PLoS ONE |
| title | Hematopoietic sphingosine 1-phosphate lyase deficiency decreases atherosclerotic lesion development in LDL-receptor deficient mice. |
| title_full | Hematopoietic sphingosine 1-phosphate lyase deficiency decreases atherosclerotic lesion development in LDL-receptor deficient mice. |
| title_fullStr | Hematopoietic sphingosine 1-phosphate lyase deficiency decreases atherosclerotic lesion development in LDL-receptor deficient mice. |
| title_full_unstemmed | Hematopoietic sphingosine 1-phosphate lyase deficiency decreases atherosclerotic lesion development in LDL-receptor deficient mice. |
| title_short | Hematopoietic sphingosine 1-phosphate lyase deficiency decreases atherosclerotic lesion development in LDL-receptor deficient mice. |
| title_sort | hematopoietic sphingosine 1 phosphate lyase deficiency decreases atherosclerotic lesion development in ldl receptor deficient mice |
| url | http://europepmc.org/articles/PMC3659045?pdf=render |
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