Neutrophil Sphingosine 1-Phosphate and Lysophosphatidic Acid Receptors in Pneumonia

Rahaman, Md. Matiur; Costello, Richard W.; Belmonte, Kristen E.; Gendy, Samir S.; Walsh, Marie Therese

doi:10.1165/rcmb.2005-0126oc

Cited by 52 publications

(60 citation statements)

References 45 publications

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“…A number of G protein-coupled receptors capable of mediating S1P signaling have been described, and we and others have been able to detect mRNA for S1P2, S1P3, and S1P4 in PMN (30). However, it is unlikely that ligation of GPCRs was responsible for the synergistic actions of S1P on PMN responses to Fc␥ receptor ligation: (1) we were unable to inhibit responses with pertussis toxin; (2) pretreatment with S1P failed to desensitize cells to further calcium influx in response to S1P and Fc␥ receptor ligation (data not shown); and (3) the active concentration range (2.5-10 M) is higher than that reported for S1P surface receptors (31).…”

Section: Discussionmentioning

confidence: 63%

Sphingosine 1-Phosphate Enhances Fcγ Receptor-Mediated Neutrophil Activation and Recruitment under Flow Conditions

Florey

Haskard

2009

The Journal of Immunology

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Background S1P is a bioactive phospholipid released by platelets and endothelial cells that has been implicated in diverse biological functions. We hypothesized that S1P may influence immune‐complex‐mediated PMN activation. Methods and Results SIP (10μM) significantly augmented Fcγ receptor IIIb‐dependent PMN adhesion at 1.5 dynes/cm2 to a substrate coated with sub‐optimal immune complexes (without S1P 22.78 ±1.5 cells/field of view, with S1P 33.25 ±3.2, p<0.03). Using fluorescence spectrometry, we found that exogenous addition of S1P led to an enhanced neutrophil Fcγ receptor‐mediated rise in intracellular Ca2+ levels in a pertussis toxin‐independent manner, while inducing only a small Ca2+ influx by itself. Reactive oxygen species (ROS) generation was also synergistically enhanced by S1P and Fcγ receptor co‐stimulation, as shown by flow cytometry with 123‐DHR. Inhibition of ROS generation abolished calcium flux and vice‐versa, as shown using n‐acetyl cysteine and EGTA respectively. Conclusions These data indicate that S1P augments neutrophil activation in response to Fc receptor ligation, with an interdependent signaling loop involving increased intracellular Ca2+ levels and ROS generation. Taken together, S1P from activated platelets or endothelial cells may serve to amplify leukocyte recruitment and tissue injury at sites of immune complex deposition in vasculitis.

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Section: Discussionmentioning

confidence: 63%

Sphingosine 1-Phosphate Enhances Fcγ Receptor-Mediated Neutrophil Activation and Recruitment under Flow Conditions

Florey

Haskard

2009

The Journal of Immunology

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“…It is possible that the LPS-induced increase in LPA receptor expression is the result of neutrophil influx. LPA receptors are expressed in neutrophils, and upregulation of LPA 1 and LPA 2 expression in neutrophils from pneumonia patients has been reported (29). Further studies are necessary to clarify the mechanisms of increased LPA receptor expression by LPS in lung tissues.…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidic acid receptor 1 modulates lipopolysaccharide-induced inflammation in alveolar epithelial cells and murine lungs

Zhao

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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-Lysophosphatidic acid (LPA), a bioactive phospholipid, plays an important role in lung inflammation by inducing the release of chemokines and lipid mediators. Our previous studies have shown that LPA induces the secretion of interleukin-8 and prostaglandin E 2 in lung epithelial cells. Here, we demonstrate that LPA receptors contribute to lipopolysaccharide (LPS)-induced inflammation. Pretreatment with LPA receptor antagonist Ki16425 or downregulation of LPA receptor 1 (LPA 1) by small-interfering RNA (siRNA) attenuated LPS-induced phosphorylation of p38 MAPK, I-B kinase, and I-B in MLE12 epithelial cells. In addition, the blocking of LPA 1 also suppressed LPS-induced IL-6 production. Furthermore, LPS treatment promoted interaction between LPA 1 and CD14, a LPS coreceptor, in a time-and dose-dependent manner. Disruption of lipid rafts attenuated the interaction between LPA 1 and CD14. Mice challenged with LPS increased plasma LPA levels and enhanced expression of LPA receptors in lung tissues. To further investigate the role of LPA receptors in LPSinduced inflammation, wild-type, or LPA 1-deficient mice, or wildtype mice pretreated with Ki16425 were intratracheally challenged with LPS for 24 h. Knock down or inhibition of LPA 1 decreased LPS-induced IL-6 release in bronchoalveolar lavage (BAL) fluids and infiltration of cells into alveolar space compared with wild-type mice. However, no significant differences in total protein concentration in BAL fluids were observed. These results showed that knock down or inhibition of LPA1 offered significant protection against LPS-induced lung inflammation but not against pulmonary leak as observed in the murine model for lung injury. lysophospholipid; signal transduction; lipopolysaccharide; inflammation; acute lung injury; lysophosphatidic acid receptor 1; interleukin-6 ACUTE LUNG INJURY (ALI) is characterized by acute respiratory failure resulting from destruction of the epithelium-capillary interface, inflammation, and extravasations of protein-rich fluid (14,26,35). The lung epithelium is the site of first contact for both inflammatory and inhaled physical environmental stimuli, acting as a physical barrier between lung interstitium and environment (30,34). Disruption of epithelial barrier integrity results in paracellular leakage of relatively large proteins, such as albumin and immunoglobulin G, into alveolar spaces (15,18,19). Thus, the epithelium not only functions as a barrier but also secretes cytokines, chemokines, and lipid mediators to attract and activate a number of resident and infiltrating cells that play a role in airway inflammation (21, 25). Our previous studies have shown that bronchial epithelial cells release interleukin (IL)-8 (7, 43, 48), IL-6 (49), and prostaglandin E 2 (PGE 2 ) (17, 47) in response to bioactive lipid mediators and lipopolysaccharide (LPS), resulting in the infiltration of neutrophils into alveolar space (7, 47). The LPS-induced murine model of lung injury has been widely used to investigate mechanisms of ALI (18,31,40). Intratra...

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“…Ceramidase can convert ceramide to sphingosine, which in turn is phosphorylated to sphingosine-1-phosphate (S1P) by sphingosine kinase. S1P has an established role in cellular migration, binding to a family of receptors (Edg) that stimulate migration in many cell types, including PMNs (43,44). Sphingosine kinase was also implicated in PMN priming, Ca 21 signaling, and migration (45).…”

Section: Discussionmentioning

confidence: 99%

An Obligate Role for Membrane-Associated Neutral Sphingomyelinase Activity in Orienting Chemotactic Migration of Human Neutrophils

Sitrin¹,

Sassanella²,

Petty³

2011

Am J Respir Cell Mol Biol

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Neutrophil Sphingosine 1-Phosphate and Lysophosphatidic Acid Receptors in Pneumonia

Cited by 52 publications

References 45 publications

Sphingosine 1-Phosphate Enhances Fcγ Receptor-Mediated Neutrophil Activation and Recruitment under Flow Conditions

Sphingosine 1-Phosphate Enhances Fcγ Receptor-Mediated Neutrophil Activation and Recruitment under Flow Conditions

Lysophosphatidic acid receptor 1 modulates lipopolysaccharide-induced inflammation in alveolar epithelial cells and murine lungs

An Obligate Role for Membrane-Associated Neutral Sphingomyelinase Activity in Orienting Chemotactic Migration of Human Neutrophils

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