Sphingosine 1-phosphate

Sphingosine 1-phosphate is a lipid of Sphingolipids (SP) class. Sphingosine 1-phosphate is associated with abnormalities such as Infection, Painful Bladder Syndrome, Atherosclerosis, Hyperglycemia and Rheumatoid Arthritis. The involved functions are known as Phosphorylation, Regulation, enzyme activity, Energy Absorption and Vascular Permeability. Sphingosine 1-phosphate often locates in Endothelium, Tissue membrane, Vascular System, Protoplasm and Microfilaments. The associated genes with Sphingosine 1-phosphate are MBTPS1 gene, FBXL15 gene, TEK gene, NTRK1 gene and Gene Family. The related lipids are Promega, Lipopolysaccharides, lysophosphatidic acid, Lysophosphatidylcholines and Lysophospholipids. The related experimental models are Knock-out, Mouse Model, Transgenic Model, Disease model and Experimental Autoimmune Encephalomyelitis.

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Introduction

To understand associated biological information of Sphingosine 1-phosphate, we collected biological information of abnormalities, associated pathways, cellular/molecular locations, biological functions, related genes/proteins, lipids and common seen animal/experimental models with organized paragraphs from literatures.

What diseases are associated with Sphingosine 1-phosphate?

Sphingosine 1-phosphate is suspected in Lymphopenia, Ischemia, Infection, Atherosclerosis, Multiple Sclerosis, Asthma and other diseases in descending order of the highest number of associated sentences.

Related references are mostly published in these journals:

Disease Cross reference Weighted score Related literature
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Possible diseases from mapped MeSH terms on references

We collected disease MeSH terms mapped to the references associated with Sphingosine 1-phosphate

MeSH term MeSH ID Detail
Respiratory Distress Syndrome, Adult D012128 15 associated lipids
Nerve Degeneration D009410 53 associated lipids
Hypertension D006973 115 associated lipids
Diabetic Angiopathies D003925 20 associated lipids
Thrombocythemia, Essential D013920 9 associated lipids
Neoplasms, Hormone-Dependent D009376 23 associated lipids
Hyperalgesia D006930 42 associated lipids
Anaphylaxis D000707 35 associated lipids
Thrombocytopenia D013921 15 associated lipids
Coronary Artery Disease D003324 47 associated lipids
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PubChem Associated disorders and diseases

What pathways are associated with Sphingosine 1-phosphate

Lipid pathways are not clear in current pathway databases. We organized associated pathways with Sphingosine 1-phosphate through full-text articles, including metabolic pathways or pathways of biological mechanisms.

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Pathway name Related literatures
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PubChem Biomolecular Interactions and Pathways

Link to PubChem Biomolecular Interactions and Pathways

What cellular locations are associated with Sphingosine 1-phosphate?

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Location Cross reference Weighted score Related literatures
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What functions are associated with Sphingosine 1-phosphate?


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Function Cross reference Weighted score Related literatures

What lipids are associated with Sphingosine 1-phosphate?

Related references are published most in these journals:

Lipid concept Cross reference Weighted score Related literatures
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What genes are associated with Sphingosine 1-phosphate?

Related references are published most in these journals:


Gene Cross reference Weighted score Related literatures

What common seen animal models are associated with Sphingosine 1-phosphate?

Knock-out

Knock-out are used in the study 'Sphingosine 1-phosphate-dependent trafficking of peritoneal B cells requires functional NFkappaB-inducing kinase in stromal cells.' (Kunisawa J et al., 2008), Knock-out are used in the study 'Connective tissue growth factor (CTGF/CCN2) mediates angiogenic effect of S1P in human dermal microvascular endothelial cells.' (Markiewicz M et al., 2011), Knock-out are used in the study 'Chasing sphingosine-1-phosphate, a lipid mediator for cardiomyocyte survival.' (Yang Q, 2007), Knock-out are used in the study 'Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function.' (Idzko M et al., 2006) and Knock-out are used in the study 'Platelet endothelial cell adhesion molecule-1 modulates endothelial cell motility through the small G-protein Rho.' (Gratzinger D et al., 2003).

Mouse Model

Mouse Model are used in the study 'Regulation of the micromechanical properties of pulmonary endothelium by S1P and thrombin: role of cortactin.' (Arce FT et al., 2008), Mouse Model are used in the study 'Sequential delivery of vascular endothelial growth factor and sphingosine 1-phosphate for angiogenesis.' (Tengood JE et al., 2010), Mouse Model are used in the study 'S1P(5) is required for sphingosine 1-phosphate-induced autophagy in human prostate cancer PC-3 cells.' (Chang CL et al., 2009), Mouse Model are used in the study 'Sphingosine-1-phosphate induces an antiinflammatory phenotype in macrophages.' (Hughes JE et al., 2008) and Mouse Model are used in the study 'The alliance of sphingosine-1-phosphate and its receptors in immunity.' (Rivera J et al., 2008).

Transgenic Model

Transgenic Model are used in the study 'Role for matrix metalloproteinase-2 in oxidized low-density lipoprotein-induced activation of the sphingomyelin/ceramide pathway and smooth muscle cell proliferation.' (Augé N et al., 2004), Transgenic Model are used in the study 'Sphingosine-1-phosphate antibodies as potential agents in the treatment of cancer and age-related macular degeneration.' (Sabbadini RA, 2011) and Transgenic Model are used in the study 'Still benched on its way to the bedside: sphingosine kinase 1 as an emerging target in cancer chemotherapy.' (Gault CR and Obeid LM, 2011).

Related references are published most in these journals:

Model Cross reference Weighted score Related literatures
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NCBI Entrez Crosslinks

All references with Sphingosine 1-phosphate

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Authors Title Published Journal PubMed Link
Dong T et al. Cortisol-induced immune suppression by a blockade of lymphocyte egress in traumatic brain injury. 2016 J Neuroinflammation pmid:27561600
Kułakowska A et al. Increased levels of sphingosine-1-phosphate in cerebrospinal fluid of patients diagnosed with tick-borne encephalitis. 2014 J Neuroinflammation pmid:25421616
Hoffmann FS et al. Fingolimod induces neuroprotective factors in human astrocytes. 2015 J Neuroinflammation pmid:26419927
Li C et al. Sphingosine 1-phosphate enhances the excitability of rat sensory neurons through activation of sphingosine 1-phosphate receptors 1 and/or 3. 2015 J Neuroinflammation pmid:25880547
He X et al. Sphingosine-1-phosphate mediates proliferation maintaining the multipotency of human adult bone marrow and adipose tissue-derived stem cells. 2010 J Mol Cell Biol pmid:20584786
Nagahashi M et al. Interstitial Fluid Sphingosine-1-Phosphate in Murine Mammary Gland and Cancer and Human Breast Tissue and Cancer Determined by Novel Methods. 2016 J Mammary Gland Biol Neoplasia pmid:27194029
Spiegel S Sphingosine and sphingosine 1-phosphate in cellular proliferation: relationship with protein kinase C and phosphatidic acid. 1993 J Lipid Mediat pmid:8268463
Rokka J et al. 19F/18F exchange synthesis for a novel [18F]S1P3-radiopharmaceutical. 2013 J Labelled Comp Radiopharm pmid:24285478
Komatsu I et al. Dupuytren's fibroblast contractility by sphingosine-1-phosphate is mediated through non-muscle myosin II. 2010 J Hand Surg Am pmid:20888494
Howard C et al. Dental pulp stem cell migration. 2010 J Endod pmid:21092813
Kurek K et al. Inhibition of Ceramide De Novo Synthesis Ameliorates Diet Induced Skeletal Muscles Insulin Resistance. 2015 J Diabetes Res pmid:26380311
Rohatagi S et al. Use of an exposure-response model to aid early drug development of an oral sphingosine 1-phosphate receptor modulator. 2009 J Clin Pharmacol pmid:18948412
Egom EE Sphingosine-1-phosphate signalling as a therapeutic target for patients with abnormal glucose metabolism and ischaemic heart disease. 2014 J Cardiovasc Med (Hagerstown) pmid:23839592
Tabasinezhad M et al. Sphingosin 1-phosphate contributes in tumor progression. J Cancer Res Ther pmid:24518696
Southern C et al. Screening β-arrestin recruitment for the identification of natural ligands for orphan G-protein-coupled receptors. 2013 J Biomol Screen pmid:23396314
Wetter JA et al. Utilization of the Tango beta-arrestin recruitment technology for cell-based EDG receptor assay development and interrogation. 2009 J Biomol Screen pmid:19726785
Highkin MK et al. High-throughput screening assay for sphingosine kinase inhibitors in whole blood using RapidFire® mass spectrometry. 2011 J Biomol Screen pmid:21297110
Niedernberg A et al. Comparative analysis of functional assays for characterization of agonist ligands at G protein-coupled receptors. 2003 J Biomol Screen pmid:14567777
Alford SK et al. Endothelial cell migration in human plasma is enhanced by a narrow range of added sphingosine 1-phosphate: implications for biomaterials design. 2009 J Biomed Mater Res A pmid:18286622
Kim YH and Tabata Y Recruitment of mesenchymal stem cells and macrophages by dual release of stromal cell-derived factor-1 and a macrophage recruitment agent enhances wound closure. 2016 J Biomed Mater Res A pmid:26704185
Marycz K et al. The influence of metal-based biomaterials functionalized with sphingosine-1-phosphate on the cellular response and osteogenic differentaion potenial of human adipose derived mesenchymal stem cells in vitro. 2016 J Biomater Appl pmid:26801473
Leclercq TM and Pitson SM Cellular signalling by sphingosine kinase and sphingosine 1-phosphate. 2006 IUBMB Life pmid:16916784
García-Sáinz JA et al. Mechanisms involved in α1B-adrenoceptor desensitization. 2011 IUBMB Life pmid:21815242
Chawla S et al. S1P prophylaxis mitigates acute hypobaric hypoxia-induced molecular, biochemical, and metabolic disturbances: A preclinical report. 2016 IUBMB Life pmid:26959531
Siess W et al. Lysophosphatidic acid and sphingosine 1-phosphate: two lipid villains provoking cardiovascular diseases? 2000 IUBMB Life pmid:10868905
Kim JH et al. Sphingosine 1-phosphate activates Erk-1/-2 by transactivating epidermal growth factor receptor in rat-2 cells. 2000 IUBMB Life pmid:11185956
Meacci E et al. Sphingosine 1-phosphate signal transduction in muscle cells. 2003 Ital. J. Biochem. pmid:12833634
Sabbadini RA et al. The role of sphingolipids in the control of skeletal muscle function: a review. 1999 Ital J Neurol Sci pmid:10937863
Lee H et al. 4-Deoxypyridoxine improves the viability of isolated pancreatic islets ex vivo. 2013 May-Jun Islets pmid:23756681
Boussommier-Calleja A et al. Pharmacologic manipulation of conventional outflow facility in ex vivo mouse eyes. 2012 Invest. Ophthalmol. Vis. Sci. pmid:22807298
Miranda GE et al. Sphingosine-1-phosphate is a key regulator of proliferation and differentiation in retina photoreceptors. 2009 Invest. Ophthalmol. Vis. Sci. pmid:19357361
Kim SE et al. The Role of Sphingosine-1-Phosphate in Adipogenesis of Graves' Orbitopathy. 2016 Invest. Ophthalmol. Vis. Sci. pmid:26830367
Wang J et al. Receptor-mediated activation of a Cl(-) current by LPA and S1P in cultured corneal keratocytes. 2002 Invest. Ophthalmol. Vis. Sci. pmid:12356825
Qiao Y et al. Sphingosine 1-phosphate elicits proinflammatory responses in ARPE-19 cells. 2012 Invest. Ophthalmol. Vis. Sci. pmid:23150617
Simón MV et al. Sphingosine-1-Phosphate Is a Crucial Signal for Migration of Retina Müller Glial Cells. 2015 Invest. Ophthalmol. Vis. Sci. pmid:26325420
Yin F and Watsky MA LPA and S1P increase corneal epithelial and endothelial cell transcellular resistance. 2005 Invest. Ophthalmol. Vis. Sci. pmid:15914605
Abrahan CE et al. Synthesis of sphingosine is essential for oxidative stress-induced apoptosis of photoreceptors. 2010 Invest. Ophthalmol. Vis. Sci. pmid:19797232
Sumida GM and Stamer WD Sphingosine-1-phosphate enhancement of cortical actomyosin organization in cultured human Schlemm's canal endothelial cell monolayers. 2010 Invest. Ophthalmol. Vis. Sci. pmid:20592229
Ko J et al. Sphingosine-1-Phosphate Mediates Fibrosis in Orbital Fibroblasts in Graves' Orbitopathy. 2017 Invest. Ophthalmol. Vis. Sci. pmid:28492873
Aoyama-Araki Y et al. Sphingosine-1-Phosphate (S1P)-Related Response of Human Conjunctival Fibroblasts After Filtration Surgery for Glaucoma. 2017 Invest. Ophthalmol. Vis. Sci. pmid:28418499
Durham JT et al. Pericyte chemomechanics and the angiogenic switch: insights into the pathogenesis of proliferative diabetic retinopathy? 2015 Invest. Ophthalmol. Vis. Sci. pmid:26030100
Ling B et al. Sphingosine-1-phosphate: a potential therapeutic agent against human breast cancer. 2011 Invest New Drugs pmid:20041340
Babahosseini H et al. Bioactive sphingolipid metabolites modulate ovarian cancer cell structural mechanics. 2013 Integr Biol (Camb) pmid:24056950
Salmanzadeh A et al. Sphingolipid metabolites modulate dielectric characteristics of cells in a mouse ovarian cancer progression model. 2013 Integr Biol (Camb) pmid:23609351
Lim SH et al. Complementary effects of ciclopirox olamine, a prolyl hydroxylase inhibitor and sphingosine 1-phosphate on fibroblasts and endothelial cells in driving capillary sprouting. 2013 Integr Biol (Camb) pmid:24190477
Won J and Lee GH T-cell-targeted signaling inhibitors. 2008 Jan-Apr Int. Rev. Immunol. pmid:18300054
Lagadari M et al. Sphingosine-1-phosphate inhibits the cytotoxic activity of NK cells via Gs protein-mediated signalling. 2009 Int. J. Oncol. pmid:19082500
Hsu A et al. Sphingosine-1-phosphate receptor-3 signaling up-regulates epidermal growth factor receptor and enhances epidermal growth factor receptor-mediated carcinogenic activities in cultured lung adenocarcinoma cells. 2012 Int. J. Oncol. pmid:22344462
Ng ML et al. The role of sphingolipid signalling in diabetes‑associated pathologies (Review). 2017 Int. J. Mol. Med. pmid:28075451
Moon MH et al. Sphingosine-1-phosphate inhibits interleukin-1β-induced inflammation in human articular chondrocytes. 2012 Int. J. Mol. Med. pmid:22992945
Renkl A et al. Distinct effects of sphingosine-1-phosphate, lysophosphatidic acid and histamine in human and mouse dendritic cells. 2004 Int. J. Mol. Med. pmid:14719124
Lim J et al. Valproic acid enforces the priming effect of sphingosine-1 phosphate on human mesenchymal stem cells. 2017 Int. J. Mol. Med. pmid:28677769
Chen W et al. Sphingosine 1-phosphate in metabolic syndrome (Review). 2016 Int. J. Mol. Med. pmid:27600830
Minamitani C et al. Involvement of Rho-kinase in sphingosine 1-phosphate-stimulated HSP27 induction in osteoblasts. 2009 Int. J. Mol. Med. pmid:19513538
Natsume H et al. (-)-Epigallocatechin gallate attenuates the induction of HSP27 stimulated by sphingosine 1-phosphate via suppression of phosphatidylinositol 3-kinase/Akt pathway in osteoblasts. 2009 Int. J. Mol. Med. pmid:19578793
Ishitsuka A et al. FTY720 and cisplatin synergistically induce the death of cisplatin-resistant melanoma cells through the downregulation of the PI3K pathway and the decrease in epidermal growth factor receptor expression. 2014 Int. J. Mol. Med. pmid:25109763
Moon MH et al. Sphingosine-1-phosphate inhibits the adipogenic differentiation of 3T3-L1 preadipocytes. 2014 Int. J. Mol. Med. pmid:25050633
Lee YJ et al. Sphingosine-1-phosphate protects against bisphosphonate‑induced HUVEC cell death via regulation of c-Jun‑N‑terminal kinase signaling. 2013 Int. J. Mol. Med. pmid:23381659
Sobue S et al. Implications of sphingosine kinase 1 expression level for the cellular sphingolipid rheostat: relevance as a marker for daunorubicin sensitivity of leukemia cells. 2008 Int. J. Hematol. pmid:18283525
Polzin A et al. Aspirin inhibits release of platelet-derived sphingosine-1-phosphate in acute myocardial infarction. 2013 Int. J. Cardiol. pmid:24169533
Lee KP et al. DJ-1-mediated upregulation of serine palmitoyltransferase 2 controls vascular neointima via S1P autocrine. 2015 Int. J. Cardiol. pmid:25978603
Ohotski J et al. Identification of novel functional and spatial associations between sphingosine kinase 1, sphingosine 1-phosphate receptors and other signaling proteins that affect prognostic outcome in estrogen receptor-positive breast cancer. 2013 Int. J. Cancer pmid:22733311
Beckham TH et al. Acid ceramidase-mediated production of sphingosine 1-phosphate promotes prostate cancer invasion through upregulation of cathepsin B. 2012 Int. J. Cancer pmid:22322590
Weigert A et al. Sphingosine kinase 2 deficient tumor xenografts show impaired growth and fail to polarize macrophages towards an anti-inflammatory phenotype. 2009 Int. J. Cancer pmid:19618460
Wang S et al. A polysaccharides MDG-1 augments survival in the ischemic heart by inducing S1P release and S1P1 expression. 2012 Int. J. Biol. Macromol. pmid:22197795
Zebol JR et al. The CCT/TRiC chaperonin is required for maturation of sphingosine kinase 1. 2009 Int. J. Biochem. Cell Biol. pmid:18775504
Korbelik M et al. Ceramide and sphingosine-1-phosphate act as photodynamic therapy-elicited damage-associated molecular patterns: cell surface exposure. 2014 Int. Immunopharmacol. pmid:24713544
Beyer T and Meyer-Hermann M Mechanisms of organogenesis of primary lymphoid follicles. 2008 Int. Immunol. pmid:18334502
Jung ID et al. Sphingosine kinase inhibitor suppresses a Th1 polarization via the inhibition of immunostimulatory activity in murine bone marrow-derived dendritic cells. 2007 Int. Immunol. pmid:17307797
Maeda Y et al. S1P lyase in thymic perivascular spaces promotes egress of mature thymocytes via up-regulation of S1P receptor 1. 2014 Int. Immunol. pmid:24343820
Setoguchi R IL-15 boosts the function and migration of human terminally differentiated CD8+ T cells by inducing a unique gene signature. 2016 Int. Immunol. pmid:26857736
Maeda Y et al. Sphingosine 1-phosphate receptor type 1 regulates egress of mature T cells from mouse bone marrow. 2010 Int. Immunol. pmid:20497959
Baranowski M et al. Ultramarathon run markedly reduces plasma sphingosine-1-phosphate concentration. 2014 Int J Sport Nutr Exerc Metab pmid:24092763
Masuko K et al. Sphingosine-1-phosphate modulates expression of vascular endothelial growth factor in human articular chondrocytes: a possible new role in arthritis. 2012 Int J Rheum Dis pmid:22898216
Gil-Ortega M et al. Ex vivo microperfusion system of the adipose organ: a new approach to studying the mobilization of adipose cell populations. 2014 Int J Obes (Lond) pmid:24357852
Ueda N Ceramide-induced apoptosis in renal tubular cells: a role of mitochondria and sphingosine-1-phoshate. 2015 Int J Mol Sci pmid:25751724
Smith P et al. Sphingosine 1-Phosphate Signaling and Its Pharmacological Modulation in Allogeneic Hematopoietic Stem Cell Transplantation. 2017 Int J Mol Sci pmid:28934113
Haddadi N et al. "Dicing and Splicing" Sphingosine Kinase and Relevance to Cancer. 2017 Int J Mol Sci pmid:28869494
Egom EE et al. Determination of Sphingosine-1-Phosphate in Human Plasma Using Liquid Chromatography Coupled with Q-Tof Mass Spectrometry. 2017 Int J Mol Sci pmid:28820460
Hajny S and Christoffersen C A Novel Perspective on the ApoM-S1P Axis, Highlighting the Metabolism of ApoM and Its Role in Liver Fibrosis and Neuroinflammation. 2017 Int J Mol Sci pmid:28749426
Koch A et al. Vitamin D Supplementation Enhances C18(dihydro)ceramide Levels in Type 2 Diabetes Patients. 2017 Int J Mol Sci pmid:28714882
Wollny T et al. Sphingosine-1-Phosphate Metabolism and Its Role in the Development of Inflammatory Bowel Disease. 2017 Int J Mol Sci pmid:28362332
Costello RW et al. Mechanism of sphingosine 1-phosphate- and lysophosphatidic acid-induced up-regulation of adhesion molecules and eosinophil chemoattractant in nerve cells. 2011 Int J Mol Sci pmid:21686182
Tokumura A et al. Elevated serum levels of arachidonoyl-lysophosphatidic acid and sphingosine 1-phosphate in systemic sclerosis. 2009 Int J Med Sci pmid:19521548
Sali M et al. Exploiting immunotherapy in Mycobacterium tuberculosis-infected mice: sphingosine 1-phosphate treatment results in a protective or detrimental effect depending on the stage of infection. 2009 Jan-Mar Int J Immunopathol Pharmacol pmid:19309565
Tian H and Yu Z Resveratrol induces apoptosis of leukemia cell line K562 by modulation of sphingosine kinase-1 pathway. 2015 Int J Clin Exp Pathol pmid:26045781
Pan HY et al. Sphingosine-1-phosphate mediates AKT/ERK maintenance of dental pulp homoeostasis. 2015 Int Endod J pmid:24931601
BÅ‚ogowski W et al. Perioperative release of pro-regenerative biochemical signals from human renal allografts subjected to ischemia-reperfusion injury. 2014 Innate Immun pmid:23608824
Yu H et al. Sphingosine kinase 1 improves cutaneous wound healing in diabetic rats. 2014 Injury pmid:24685054
Ding R et al. Sphingosine-1-phosphate attenuates lung injury induced by intestinal ischemia/reperfusion in mice: role of inducible nitric-oxide synthase. 2012 Inflammation pmid:21302134
Miyabe C et al. A sphingosine 1-phosphate receptor agonist ameliorates animal model of vasculitis. 2017 Inflamm. Res. pmid:27942751
Lv M et al. Sphingosine kinase 1/sphingosine-1-phosphate regulates the expression of interleukin-17A in activated microglia in cerebral ischemia/reperfusion. 2016 Inflamm. Res. pmid:27002656
Seo Y et al. Sphingosine-1-phosphate is involved in inflammatory reactions in patients with Graves' orbitopathy. 2017 Inflamm. Res. pmid:28364200
Farnoud AM et al. The Granuloma Response Controlling Cryptococcosis in Mice Depends on the Sphingosine Kinase 1-Sphingosine 1-Phosphate Pathway. 2015 Infect. Immun. pmid:25895971
Fournie P et al. Sphingosine-1 phosphate prevents ethanol-induced corneal epithelial apoptosis. 2012 Mar-Apr Indian J Ophthalmol pmid:22446906
Sordillo PP et al. Review: The Prolonged QT Interval: Role of Pro-inflammatory Cytokines, Reactive Oxygen Species and the Ceramide and Sphingosine-1 Phosphate Pathways. In Vivo pmid:26546519
Thamilselvan V et al. Sphingosine-1-phosphate stimulates human Caco-2 intestinal epithelial proliferation via p38 activation and activates ERK by an independent mechanism. 2002 In Vitro Cell. Dev. Biol. Anim. pmid:12197778
Greco E et al. Natural lysophospholipids reduce Mycobacterium tuberculosis-induced cytotoxicity and induce anti-mycobacterial activity by a phagolysosome maturation-dependent mechanism in A549 type II alveolar epithelial cells. 2010 Immunology pmid:19878354
Turner VM and Mabbott NA Ageing adversely affects the migration and function of marginal zone B cells. 2017 Immunology pmid:28369800
Schulz C et al. Hematopoietic stem and progenitor cells: their mobilization and homing to bone marrow and peripheral tissue. 2009 Immunol. Res. pmid:19340403