The role of the lysophospholipid sphingosine 1-phosphate in immune cell biology

2006 ◽  
Vol 54 (4) ◽  
pp. 239-251 ◽  
Author(s):  
Henrik von Wenckstern ◽  
Karsten Zimmermann ◽  
Burkhard Kleuser
Keyword(s):  
Cell Biology ◽  
Immune Cell ◽  
Sphingosine 1 Phosphate

scholarly journals The Role of Platelets in Cancer Pathophysiology: Focus on Malignant Glioma

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 569 ◽  
Author(s):  
Sascha Marx ◽  
Yong Xiao ◽  
Marcel Baschin ◽  
Maximilian Splittstöhser ◽  
Robert Altmann ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Immune Cells ◽  
Potential Role ◽  
Immune Cell ◽  
Malignant Gliomas ◽  
Cell Communication ◽  
Distant Metastases ◽  
Sphingosine 1 Phosphate ◽  
The Central Nervous System

The link between thrombocytosis and malignancy has been well known for many years and its associations with worse outcomes have been reported mainly for solid tumors. Besides measuring platelet count, it has become popular to assess platelet function in the context of malignant diseases during the last decade. Malignant gliomas differ tremendously from malignancies outside the central nervous system because they virtually never form distant metastases. This review summarizes the current understanding of the platelet–immune cell communication and its potential role in glioma resistance and progression. Particularly, we focus on platelet-derived proinflammatory modulators, such as sphingosine-1-phosphate (S1P). The multifaceted interaction with immune cells puts the platelet into an interesting perspective regarding the recent advances in immunotherapeutic approaches in malignant glioma.

scholarly journals Inorganic polyphosphate potentiates lipopolysaccharide-induced macrophage inflammatory response

2020 ◽  
Vol 295 (12) ◽  
pp. 4014-4023
Author(s):  
Toru Ito ◽  
Suguru Yamamoto ◽  
Keiichi Yamaguchi ◽  
Mami Sato ◽  
Yoshikatsu Kaneko ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cell Biology ◽  
Immune Cell ◽  
Critical Role ◽  
Binding Assays ◽  
Inorganic Polyphosphate ◽  
Cell Dysfunction ◽  
Factor Α

Inorganic polyphosphate (polyP) is a linear polymer of orthophosphate units that are linked by phosphoanhydride bonds and is involved in various pathophysiological processes. However, the role of polyP in immune cell dysfunction is not well-understood. In this study, using several biochemical and cell biology approaches, including cytokine assays, immunofluorescence microscopy, receptor-binding assays with quartz crystal microbalance, and dynamic light scanning, we investigated the effect of polyP on in vitro lipopolysaccharide (LPS)-induced macrophage inflammatory response. PolyP up-regulated LPS-induced production of the inflammatory cytokines, such as tumor necrosis factor α, interleukin-1β, and interleukin-6, in macrophages, and the effect was polyP dose– and chain length–dependent. However, orthophosphate did not exhibit this effect. PolyP enhanced the LPS-induced intracellular macrophage inflammatory signals. Affinity analysis revealed that polyP interacts with LPS, inducing formation of small micelles, and the polyP-LPS complex enhanced the binding affinity of LPS to Toll-like receptor 4 (TLR4) on macrophages. These results suggest that inorganic polyP plays a critical role in promoting inflammatory response by enhancing the interaction between LPS and TLR4 in macrophages.

scholarly journals Beyond Immune Cell Migration: The Emerging Role of the Sphingosine-1-phosphate Receptor S1PR4 as a Modulator of Innate Immune Cell Activation

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Catherine Olesch ◽  
Christian Ringel ◽  
Bernhard Brüne ◽  
Andreas Weigert
Keyword(s):  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Diverse Range ◽  
Therapeutic Implications ◽  
Receptor Repertoire ◽  
Sphingosine 1 Phosphate ◽  
Specific Outcome ◽  
Important Regulator

The sphingolipid sphingosine-1-phosphate (S1P) emerges as an important regulator of immunity, mainly by signaling through a family of five specific G protein-coupled receptors (S1PR1–5). While S1P signaling generally has the potential to affect not only trafficking but also differentiation, activation, and survival of a diverse range of immune cells, the specific outcome depends on the S1P receptor repertoire expressed on a given cell. Among the S1PRs, S1PR4 is specifically abundant in immune cells, suggesting a major role of the S1P/S1PR4 axis in immunity. Recent studies indeed highlight its role in activation of immune cells, differentiation, and, potentially, trafficking. In this review, we summarize the emerging data that support a major role of S1PR4 in modulating immunity in humans and mice and discuss therapeutic implications.

scholarly journals The Scribble Complex PDZ Proteins in Immune Cell Polarities

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Dante Barreda ◽  
Luis H. Gutiérrez-González ◽  
Erasmo Martínez-Cordero ◽  
Carlos Cabello-Gutiérrez ◽  
Rommel Chacón-Salinas ◽  
...  
Keyword(s):  
Immune System ◽  
T Cell Activation ◽  
Cell Biology ◽  
Cell Activation ◽  
Immune Cell ◽  
Immunological Synapse ◽  
Cell Polarization ◽  
Cell Functions ◽  
Wide Range

hScrib and hDlg belong to the PDZ family of proteins. Since the identification of these highly phylogenetically conserved scaffolds, an increasing amount of experiments has elucidated the roles of hScrib and hDlg in a variety of cell functions. Remarkably, their participation during the establishment of polarity in epithelial cells is well documented. Although the role of both proteins in the immune system is scantly known, it has become a growing field of investigation. Here, we summarize the interactions and functions of hScrib and hDlg1, which participate in diverse functions involving cell polarization in immune cells, and discuss their relevance in the immune cell biology. The fundamental role of hScrib and hDlg1 during the establishment of the immunological synapse, hence T cell activation, and the recently described role of hScrib in reactive oxygen species production in macrophages and of hDlg1 in cytokine production by dendritic cells highlight the importance of both proteins in immune cell biology. The expression of these proteins in other leukocytes can be anticipated and needs to be confirmed. Due to their multiple interaction domains, there is a wide range of possible interactions of hScrib and hDlg1 that remains to be explored in the immune system.

S1PR4 is required for plasmacytoid dendritic cell differentiation

2015 ◽  
Vol 396 (6-7) ◽  
pp. 775-782 ◽  
Author(s):  
Christina Dillmann ◽  
Javier Mora ◽  
Catherine Olesch ◽  
Bernhard Brüne ◽  
Andreas Weigert
Keyword(s):  
Dendritic Cell ◽  
Cell Biology ◽  
Cell Function ◽  
Immune Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Type I ◽  
Hematopoietic Stem ◽  
Dendritic Cell Differentiation ◽  
Sphingosine 1 Phosphate

Abstract The sphingolipid sphingosine-1-phosphate (S1P) has various functions in immune cell biology, regulating survival, proliferation, and, most prominently, migration. S1P couples to five G protein-coupled receptors (S1PR1–5) to transduce its effects on immune cell function. Expression of S1PR4 is restricted to immune cells. However, its impact on immune cell biology is largely elusive. In the current study, we intended to answer the question of whether S1P might affect plasmacytoid dendritic cell (pDC) migration, which dominantly express S1PR4. pDC are highly specialized cells producing large amounts of type I interferon in response to TLR7/9 ligands after viral infection or during autoimmunity. Surprisingly, we noticed a reduced abundance of pDC, particularly CD4- pDC, in all organs of S1PR4-deficient vs. wildtype mice. This effect was not caused by altered migration of mature pDC, but rather a reduced potential of pDC progenitors, especially common DC progenitors, to differentiate into pDCs. In vitro studies suggested that reduced S1PR4-deficient pDC progenitor differentiation into mature pDC might be explained by both migration and differentiation of pDC progenitors in the bone marrow. As S1PR4 also affected the differentiation of CD34+ human hematopoietic stem cells into pDC, interfering with S1PR4 might be useful to reduce pDC numbers during autoimmunity.

scholarly journals Extracellular Matrix Enzymes and Immune Cell Biology

2021 ◽  
Vol 8 ◽  
Author(s):  
Meagan McMahon ◽  
Siying Ye ◽  
Jess Pedrina ◽  
Daniel Dlugolenski ◽  
John Stambas
Keyword(s):  
Extracellular Matrix ◽  
Cell Biology ◽  
Cell Function ◽  
Immune Cell ◽  
Vital Role ◽  
Immune Cell Function ◽  
Immune Cell Migration ◽  
And Function ◽  
A Current

Remodelling of the extracellular matrix (ECM) by ECM metalloproteinases is increasingly being associated with regulation of immune cell function. ECM metalloproteinases, including Matrix Metalloproteinases (MMPs), A Disintegrin and Metalloproteinases (ADAMs) and ADAMs with Thombospondin-1 motifs (ADAMTS) play a vital role in pathogen defence and have been shown to influence migration of immune cells. This review provides a current summary of the role of ECM enzymes in immune cell migration and function and discusses opportunities and limitations for development of diagnostic and therapeutic strategies targeting metalloproteinase expression and activity in the context of infectious disease.

scholarly journals Mechanism of sphingosine 1-phosphate clearance from blood

2020 ◽  
Vol 477 (5) ◽  
pp. 925-935 ◽  
Author(s):  
Yugesh Kharel ◽  
Tao Huang ◽  
Anita Salamon ◽  
Thurl E. Harris ◽  
Webster L. Santos ◽  
...  
Keyword(s):  
Immune Cell ◽  
General Mechanism ◽  
Concentration Gradients ◽  
Sphingosine Kinase 2 ◽  
Sphingosine 1 Phosphate ◽  
Degradative Enzymes ◽  
High Altitude Acclimatization ◽  
Endothelial Integrity ◽  
S1p Lyase

The interplay of sphingosine 1-phosphate (S1P) synthetic and degradative enzymes as well as S1P exporters creates concentration gradients that are a fundamental to S1P biology. Extracellular S1P levels, such as in blood and lymph, are high relative to cellular S1P. The blood-tissue S1P gradient maintains endothelial integrity while local S1P gradients influence immune cell positioning. Indeed, the importance of S1P gradients was recognized initially when the mechanism of action of an S1P receptor agonist used as a medicine for multiple sclerosis was revealed to be inhibition of T-lymphocytes’ recognition of the high S1P in efferent lymph. Furthermore, the increase in erythrocyte S1P in response to hypoxia influences oxygen delivery during high altitude acclimatization. However, understanding of how S1P gradients are maintained is incomplete. For example, S1P is synthesized but is only slowly metabolized by blood yet circulating S1P turns over quickly by an unknown mechanism. Prompted by the counterintuitive observation that blood S1P increases markedly in response to inhibition S1P synthesis (by sphingosine kinase 2 (SphK2)), we studied mice wherein several tissues were made deficient in either SphK2 or S1P degrading enzymes. Our data reveal a mechanism whereby S1P is de-phosphorylated at the hepatocyte surface and the resulting sphingosine is sequestered by SphK phosphorylation and in turn degraded by intracellular S1P lyase. Thus, we identify the liver as the primary site of blood S1P clearance and provide an explanation for the role of SphK2 in this process. Our discovery suggests a general mechanism whereby S1P gradients are shaped.

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