Cutting Edge: Differential Constitutive Expression of Functional Receptors for Lysophosphatidic Acid by Human Blood Lymphocytes

Goetzl, Edward J.; Kong, Yi‐chi M.; Voice, Julia K.

doi:10.4049/jimmunol.164.10.4996

Cited by 93 publications

(91 citation statements)

References 20 publications

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“…Pathogenic mycobacteria survive in M and reside within phagosomes that do not fuse with lysosomes (26). Therefore, lysocardiolipin may be a candidate lipid involved in preventing phagolysosome fusion or suppression of CD4 T cell functions (26,31). Furthermore, lysophospholipids can influence signal transduction pathways, e.g., by stimulating arachidonic acid release and activating protein kinase C (32,33).…”

Section: Discussionmentioning

confidence: 99%

Mycobacterial Lysocardiolipin Is Exported from Phagosomes upon Cleavage of Cardiolipin by a Macrophage-Derived Lysosomal Phospholipase A2

Fischer

Chatterjee

Torrelles

et al. 2001

The Journal of Immunology

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Pathogenic mycobacteria are able to survive and proliferate in phagosomes within host macrophages (Mφ). This capability has been attributed in part to their cell wall, which consists of various unique lipids. Some of these are important in the host-pathogen interaction, such as resistance against microbicidal effector mechanisms and modulation of host cell functions, and/or are presented as Ags to T cells. Here we show that two lipids are released from the mycobacterial cell wall within the phagosome of infected Mφ and transported out of this compartment into intracellular vesicles. One of these lipids was identified as lysocardiolipin. Lysocardiolipin was generated through cleavage of mycobacterial cardiolipin by a Ca2+-independent phospholipase A2 present in Mφ lysosomes. This result indicates that lysosomal host cell enzymes can interact with released mycobacterial lipids to generate new products with a different intracellular distribution. This represents a novel pathway for the modification of bacterial lipid Ags.

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Section: Discussionmentioning

confidence: 99%

Mycobacterial Lysocardiolipin Is Exported from Phagosomes upon Cleavage of Cardiolipin by a Macrophage-Derived Lysosomal Phospholipase A2

Fischer

Chatterjee

Torrelles

et al. 2001

The Journal of Immunology

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“…S1P [1][2][3] are widely distributed, whereas S1P 4 is mainly expressed in the lymphoid tissue, and S1P 5 is restricted to the nervous system. Expression of S1PR in the immune system has been shown to vary among CD4 + and CD8 + T cells, B cells and monocytes [17].…”

Section: Introductionmentioning

confidence: 99%

The immunomodulator FTY720 interferes with effector functions of human monocyte‐derived dendritic cells

et al. 2005

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The potent immunomodulator FTY720 elicits immunosuppression via acting on sphingosine 1-phosphate receptors (S1PR), thereby leading to an entrapment of lymphocytes in the secondary lymphoid tissue. To elucidate the potential in vitro effects of this drug on human monocyte-derived DC, we used low nanomolar therapeutic concentrations of FTY720 and phosphorylated FTY720 (FTY720-P) and investigated their influence on DC surface marker expression, protein levels of S1PR and DC effector functions: antigen uptake, chemotaxis, cytokine production, allostimulatory and Thpriming capacity. We report that both FTY720 and FTY720-P reduce chemotaxis of immature and mature DC. Mature DC generated in the presence of FTY720 or FTY720-P showed an impaired immunostimmulatory capacity and reduced IL-12 but increased IL-10 production. T cells cultured in the presence of FTY720-or FTY720-P-treated DC showed an altered cytokine production profile indicating a shift from Th1 toward Th2 differentiation. In treated immature and mature DC, expression levels for two S1PR proteins, S1P 1 and S1P 4, were reduced. We conclude that in vitro treatment with FTY720 affects DC features that are essential for serving their role as antigen-presenting cells. This might represent a new aspect of the overall immunosuppressive action of FTY720 and makes DC potential targets of further sphingolipid-derived drugs.

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“…Mouse CD4 T cells were isolated from splenocytes of 6-to 8-wk-old C57BL/6 female mice at a minimum purity of 97% using metallic microbeads bearing anti-CD4 mAbs and two cycles of magnetic retention chromatography (Miltenyi Biotec, Auburn, CA), as described elsewhere (8,9). For some studies, 1-ml suspensions of purified T cells in RPMI 1640-50 g/ml fatty acid-free BSA (FAF-BSA) (Calbiochem, La Jolla, CA) with 100 U/ml penicillin G and 50 g/ml streptomycin (RPMI 1640-BSA) were activated by incubation for 24 h on 2 g each of adherent anti-CD3 plus anti-CD28 mAbs (BD PharMingen, San Diego, CA) in six-well plates.…”

Section: Isolation Activation and Fluorescent Labeling Of Mouse Splmentioning

confidence: 99%

“…Blood unstimulated CD4 T cells express high levels of LPA 2 (Edg-4) receptors constitutively, whereas CD8 T cells from the same source show only traces of LPA 1 (Edg-2) (8). In studies of regulation of expression of LPA receptors, mitogen activation of blood CD4 T cells down-regulated expression of LPA 2 and upregulated that of LPA 1 , but such activation of CD8 T cells did not alter expression of any LPA receptor (9).…”

mentioning

confidence: 99%

Cutting Edge: Suppression of T Cell Chemotaxis by Sphingosine 1-Phosphate

Graeler

Shankar²,

Goetzl

2002

The Journal of Immunology

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128

131

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Murine CD4 and CD8 T cells express predominantly types 1 and 4 sphingosine 1-phosphate (S1P) G protein-coupled receptors (designated S1P1 and S1P4 or previously endothelial differentiation gene-encoded 1 and 6) for S1P, which has a normal plasma concentration of 0.1–1 μM. S1P now is shown to enhance chemotaxis of CD4 T cells to CCL-21 and CCL-5 by up to 2.5-fold at 10 nM to 0.1 μM, whereas 0.3–3 μM S1P inhibits this chemotaxis by up to 70%. Chemotaxis of S1P1, but not S1P4, transfectants to CXCL1 and CXCL4 was similarly affected by S1P. Activation of CD4 T cells, which decreases S1P receptor expression, suppressed effects of S1P on chemotaxis. Pretreatment of labeled CD4 T cells with S1P before reintroduction into mice inhibited by a maximum of 75% their migration into chemokine-challenged s.c. air pouches. The S1P-S1P1 receptor axis thus controls recruitment of naive T cells by maintaining their response threshold to diverse lymphotactic factors.

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Cutting Edge: Differential Constitutive Expression of Functional Receptors for Lysophosphatidic Acid by Human Blood Lymphocytes

Cited by 93 publications

References 20 publications

Mycobacterial Lysocardiolipin Is Exported from Phagosomes upon Cleavage of Cardiolipin by a Macrophage-Derived Lysosomal Phospholipase A2

Mycobacterial Lysocardiolipin Is Exported from Phagosomes upon Cleavage of Cardiolipin by a Macrophage-Derived Lysosomal Phospholipase A2

The immunomodulator FTY720 interferes with effector functions of human monocyte‐derived dendritic cells

Cutting Edge: Suppression of T Cell Chemotaxis by Sphingosine 1-Phosphate

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