Leukotrienes, Sphingolipids, and Leukocyte Trafficking

Yopp, Adam C.; Randolph, Gwendolyn J.; Bromberg, Jonathan S.

doi:10.4049/jimmunol.171.1.5

Cited by 36 publications

(31 citation statements)

References 94 publications

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“…DC trafficking is determined by various factors, in particular cell maturation status, cognate G-protein-coupled receptor expression, chemokine signaling and expression of cell surface intercellular adhesion molecules (38)(39)(40). In the present study, exposure of immature BMDCs (equivalent to those that circulate in the blood) to physiologic concentrations of FTY720-P did not affect their chemokine receptor (CCR1, 5, 6 and 7) mRNA expression significantly.…”

Section: Discussionmentioning

confidence: 42%

The Sphingosine‐1‐Phosphate Receptor Agonist FTY720 Modulates Dendritic Cell Trafficking In Vivo

Lan

Creus

Colvin

et al. 2005

American Journal of Transplantation

107

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on lymphocytes, thereby inhibiting their egress from lymphoid organs and their recirculation to inflammatory sites. Potential effects on dendritic cell (DC) trafficking have not been evaluated. Here, we demonstrate the expression of all five S1PR subtypes (S1PR1-5) by murine DCs. Administration of FTY720 to C57BL/10 mice markedly reduced circulating T and B lymphocytes within 24 h, but not blood-borne DCs, which were enhanced significantly for up to 96 h, while DCs in lymph nodes and spleen were reduced. Numbers of adoptively transferred, fluorochrome-labeled syngeneic or allogeneic DCs in blood were increased significantly in FTY720-treated animals, while donorderived DCs and allostimulatory activity for host naïve T cells within the spleen were reduced. Administration of the selective S1PR1 agonist SEW2871 significantly enhanced circulating DC numbers. Flow analysis revealed that CD11b, CD31/PECAM-1, CD54/ICAM-1 and CCR7 expression on blood-borne DCs was downregulated following FTY720 administration. Transendothelial migration of FTY720-P-treated immature DCs to the CCR7 ligand CCL19 was reduced. These novel data suggest that modulation of DC trafficking by FTY720 may contribute to its immunosuppressive effects.

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Section: Discussionmentioning

confidence: 42%

The Sphingosine‐1‐Phosphate Receptor Agonist FTY720 Modulates Dendritic Cell Trafficking In Vivo

Lan

Creus

Colvin

et al. 2005

American Journal of Transplantation

107

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“…Since lipid mediators such as leukotrienes and prostaglandins can induce neutrophil migration, 41 their contribution in indirect neutrophil recruitment was evaluated. NDGA is a selective lipoxygenase inhibitor (inhibitory concentration 50% [IC 50 ], 0.2 M for 5-lipoxygenase [5-LOX and 30 M for 12-LOX and 15-LOX) and was used to inhibit leukotriene production.…”

Section: Resultsmentioning

confidence: 99%

CD1d-unrestricted human NKT cells release chemokines upon Fas engagement

Giroux

Denis

2005

Blood

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Attempts at inducing allograft immune privilege by enforced Fas ligand expression have shown accelerated rejection mediated by neutrophils. While it has been proposed that Fas ligand was directly chemotactic toward neutrophils, several lines of evidence argue for an indirect recruitment mechanism. This question was addressed by using in vitro migration assays that used highly purified human leukocyte subsets. IntroductionApoptosis plays a crucial role in development, tissue homeostasis, and immune system function. Fas-mediated apoptosis occurs through receptor oligomerization by Fas ligand (FasL), 1 leading to the recruitment of caspase-8. The auto-proteolytic activation of caspase-8 leads to executor caspase processing that, in turn, cleaves proteins essential for cell survival. Apoptotic cells are then engulfed by neighboring cells, limiting inflammation. 1 FasL expression by activated T cells is crucial to the resolution of immune responses through activation-induced cell death. 1 Besides activated T cells, FasL is expressed in immune-privileged sites, inducing apoptosis of self-reactive T cells infiltrating the site. 2 FasL expression by cancer cells has also been proposed to participate in tumor immune privilege. 3 Given the sensitivity of T cells to FasL-mediated apoptosis, it was hypothesized that enforced expression of FasL in allografts would create artificial immune privileged sites, allowing organ acceptance without having to resort to immunosuppressive drugs. 2 While enforced FasL expression prolonged allograft survival in certain models, several reports showed massive granulocyte infiltration leading to acute rejection. [4][5][6][7][8] The outcome of graft acceptance might depend on microenvironmental factors such as FasL expression levels, local cytokine expression, and cell types present near the graft site. In vitro migration assays have shown that FasL could behave as a neutrophil chemokine, 9,10 a claim disputed by others. 11,12 It is becoming increasingly clear that Fas engagement can mediate nonapoptotic signaling events, leading to cytokine and chemokine expression in different cell types. 13 For instance, serum-starved fibroblasts release interleukin 6 (IL-6) and IL-8 upon Fas engagement through transcription factor activation. 14 Caspase inhibition in Fas-treated T lymphocytes blocks apoptosis and unmasks proinflammatory cytokine release, also mediated through transcription factor activation. 15 Caspase activity has been reported to contribute to T-cell activation through selective caspase substrate cleavage in T cells without apoptosis. 16,17 Finally, naturally occurring caspase-8 mutations in humans not only prevents apoptosis but also leads to decreased T-lymphocyte activation. 18 Thus, Fas signaling and caspase activity can participate in T-cell activation and inflammatory processes.To better understand the contribution of FasL in neutrophil recruitment, in vitro migration assays were performed using cross-linked soluble FasL, since anti-Fas antibodies do not behave like the natural l...

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“…Because of the importance of leukocyte trafficking (Cotran et al 1999a), we have referred to these as local "go" and "stop" signals Takano et al 1997) or endogenous mediators of anti-inflammation and pro-resolution (Serhan 1994). These are now generally classified as "checkpoint regulators" within the innate response (Nathan 2002;Yopp et al 2003).…”

Section: Pus Bonum Et Laudabilementioning

confidence: 97%

A search for endogenous mechanisms of anti-inflammation uncovers novel chemical mediators: missing links to resolution

Serhan

2004

Histochem Cell Biol

158

131

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Multicellular responses to infection, injury, or inflammatory stimuli lead to the formation and release of a wide range of local chemical mediators by the host. The integrated response of the host is essential in health and disease, thus it is important to achieve a more complete understanding of the local cellular and molecular events that govern the formation and actions of local mediators that can serve as endogenous counter-regulatory functions in effector cells of the immune system or "endogenous local mediators of resolution." Since these compounds in theory and in experimental models of inflammation appear to control the duration and magnitude of inflammation, knowledge of their elucidation could provide new avenues for appreciating the molecular phenotypes of many inflammatory diseases. The first of these endogenous local counter-regulators recognized were the lipoxins, which are trihydroxytetraene-containing lipid mediators that can be formed during cell-cell interactions via transcellular biosynthesis. Since this circuit of lipoxin formation and action appears to be of physiological relevance for the resolution of inflammation, therapeutic modalities targeted at this system are likely to have fewer unwanted side effects acting as agonists than the inhibitor approach currently used in anti-inflammatory therapies. This chapter provides an overview of the recent knowledge about the biosynthesis and bioactions of the novel anti-inflammatory lipid mediators, resolvins, docosatrienes, and neuroprotectins, and their aspirin-triggered counterparts. These novel families of lipid-derived mediators, which carry anti-inflammatory, pro-resolving, and protective properties, were originally isolated during spontaneous resolution. These new pathways open new opportunities for appreciating the role of neutrophils in the generation of potent protective lipid mediators and protective host signaling.

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Leukotrienes, Sphingolipids, and Leukocyte Trafficking

Cited by 36 publications

References 94 publications

The Sphingosine‐1‐Phosphate Receptor Agonist FTY720 Modulates Dendritic Cell Trafficking In Vivo

The Sphingosine‐1‐Phosphate Receptor Agonist FTY720 Modulates Dendritic Cell Trafficking In Vivo

CD1d-unrestricted human NKT cells release chemokines upon Fas engagement

A search for endogenous mechanisms of anti-inflammation uncovers novel chemical mediators: missing links to resolution

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