ArticlePloS one2012
Sphingosine kinase 1 mediation of expression of the anaphylatoxin receptor C5L2 dampens the inflammatory response to endotoxin.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 28 citations in OpenAlex.
- Sphingolipid Signaling and Complement Activation in Glioblastoma: A Promising Avenue for Therapeutic Intervention.BioChem · 2024Article
- Crosstalk between pro-survival sphingolipid metabolism and complement signaling induces inflammasome-mediated tumor metastasis.Cell reports · 2022Article
- Review
- Complement Properdin Regulates the Metabolo-Inflammatory Response to a High Fat Diet.Medicina (Kaunas, Lithuania) · 2020Article
- T Cell Expression of C5a Receptor 2 Augments Murine Regulatory T Cell (TJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- Complement in ANCA-associated vasculitis: mechanisms and implications for management.Nature reviews. Nephrology · 2017Review
- The Controversial C5a Receptor C5aR2: Its Role in Health and Disease.Journal of immunology research · 2017Review
- Adipocyte lipolysis-stimulated interleukin-6 production requires sphingosine kinase 1 activity.The Journal of biological chemistry · 2014Article
- The interaction between C5a and sphingosine-1-phosphate in neutrophils for antineutrophil cytoplasmic antibody mediated activation.Arthritis research & therapy · 2014Article
- Sphingosine-1-phosphate, FTY720, and sphingosine-1-phosphate receptors in the pathobiology of acute lung injury.American journal of respiratory cell and molecular biology · 2013Review
- New developments in C5a receptor signaling.Cell health and cytoskeleton · 2012Article
- Apolipoprotein M--a new biomarker in sepsis.Critical care (London, England) · 2012Article
- Sphingolipids: a potential molecular approach to treat allergic inflammation.Journal of allergy · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The complement anaphylatoxin C5a has a pathogenetic role in endotoxin-induced lung inflammatory injury by regulating phagocytic cell migration and activation. Endotoxin and C5a activate the enzyme sphingosine kinase (Sphk) 1 to generate the signaling lipid sphingosine-1-phosphate (S1P), a critical regulator of phagocyte function. We assessed the function of Sphk1 and S1P in experimental lung inflammatory injury and determined their roles in anaphylatoxin receptor signaling and on the expression of the two C5a receptors, C5aR (CD88) and C5L2, on phagocytes. We report that Sphk1 gene deficient (Sphk1(-/-)) mice had augmented lung inflammatory response to endotoxin compared to wild type mice. Sphk1 was required for C5a-mediated reduction in cytokine and chemokine production by macrophages. Moreover, neutrophils from Sphk1(-/-) mice failed to upregulate the anaphylatoxin receptor C5L2 in response to LPS. Exogenous S1P restored C5L2 cell surface expression of Sphk1(-/-) mouse neutrophils to wild type levels but had no effect on cell surface expression of the other anaphylatoxin receptor, CD88. These results provide the first genetic evidence of the crucial role of Sphk1 in regulating the balance between expression of CD88 and C5L2 in phagocytes. S1P-mediated up-regulation of C5L2 is a novel therapeutic target for mitigating endotoxin-induced lung inflammatory injury.
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