Inhibition by pulmonary surfactant Curosurf of secretory phospholipase A2 expression in guinea-pig alveolar macrophages

Hidi, Rabiâ; Vial, Daniel; Havet, Nathalie; Berger, Arnaud; Vargaftig, B.B.; Touqui, Lhousseine

doi:10.1016/s0006-2952(97)00328-6

Cited by 11 publications

(7 citation statements)

References 10 publications

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“…In acute lung injury in rabbits, a sPLA 2 inhibitor reduced the production of LTB 4 , decreased the neutrophil count and protected surfactant hydrolysis [31] . Porcine lung surfactant, used for the treatment of RDS, downregulates the in vitro synthesis of sPLA 2 by blocking its expression at the transcriptional level [32] . Addition of SP-A to surfactant preparations inhibits sPLA 2 activity [23] and addition of a 5-lipoxygenase inhibitor to surfactant reduces lung injury in a rat lavage model of ARDS [33] .…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Secretory Phospholipase A<sub>2</sub> in Infants with Respiratory Distress Syndrome Stimulates in vitro Neutrophil Migration

Schrama

Elferink²,

Hack³

et al. 2009

Neonatology

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Background: The massive pulmonary neutrophil influx in respiratory distress syndrome (RDS) in preterm infants has been ascribed to the effect of leukotriene B₄ (LTB₄). Objectives: To investigate whether secretory phospholipase A₂ (sPLA₂), the rate-limiting enzyme in LTB₄ production, is present in lungs of RDS infants and stimulates neutrophil migration. Methods: sPLA₂ was measured in tracheal aspirates from 15 preterm infants with RDS. The effect of aspirates on cord blood neutrophil migration was first measured, and the contribution of sPLA₂ was assessed by addition of its endogenous inhibitor Clara cell protein (CC16) or absorption of sPLA₂ from the aspirates. The role of intracellular signal transduction activation and LTB₄ formation in sPLA₂-induced neutrophil migration was determined using purified sPLA₂, several inhibitors of signal transduction, a LTB₄ synthesis inhibitor and a LTB₄ receptor antagonist. Results: All aspirates contained sPLA₂, which significantly stimulated neutrophil migration. Addition of CC16 or absorption of sPLA₂ abolished the stimulatory effect. All inhibitors significantly reduced sPLA₂-induced neutrophil migration. Conclusions: sPLA₂ is present in tracheal aspirates of preterm infants with RDS. Human recombinant sPLA₂ and pancreatic type sPLA₂ stimulate in vitro cord blood neutrophil migration via activation of intracellular signal transduction pathways, LTB₄ production and receptor binding. We speculate that sPLA₂ contributes to pulmonary neutrophil influx in RDS. Further studies are needed to determine the potential of sPLA₂ inhibition as a treatment for RDS.

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Section: Discussionmentioning

confidence: 99%

Pulmonary Secretory Phospholipase A<sub>2</sub> in Infants with Respiratory Distress Syndrome Stimulates in vitro Neutrophil Migration

Schrama

Elferink²,

Hack³

et al. 2009

Neonatology

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“…Guinea pig AM, the major pulmonary source of sPLA 2 -IIA in an experimental model of ARDS (32), secrete this enzyme in vitro (29,33). We first ensured that purified recombinant gp-sPLA 2 -IIA had the same bactericidal effect against B. anthracis, and the same enzymatic activity against known substrates as recombinant human sPLA 2 -IIA (data not shown).…”

Section: Bactericidal Activity Of Spla 2 -Iia Released By Guinea Pig mentioning

confidence: 99%

High Bactericidal Efficiency of Type IIA Phospholipase A2 against Bacillus anthracis and Inhibition of Its Secretion by the Lethal Toxin

Gimenez

Payá

et al. 2004

The Journal of Immunology

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There is a considerable body of evidence supporting the role of secretory type II-A phospholipase A2 (sPLA2-IIA) as an effector of the innate immune response. This enzyme also exhibits bactericidal activity especially toward Gram-positive bacteria. In this study we examined the ability of sPLA2-IIA to kill Bacillus anthracis, the etiological agent of anthrax. Our results show that both germinated B. anthracis spores and encapsulated bacilli were sensitive to the bactericidal activity of recombinant sPLA2-IIA in vitro. In contrast, nongerminated spores were resistant. This bactericidal effect was correlated to the ability of sPLA2-IIA to hydrolyze bacterial membrane phospholipids. Guinea pig alveolar macrophages, the major source of sPLA2-IIA in an experimental model of acute lung injury, released enough sPLA2-IIA to kill extracellular B. anthracis. The production of sPLA2-IIA was significantly inhibited by B. anthracis lethal toxin. Human bronchoalveolar lavage fluids from acute respiratory distress syndrome patients are known to contain sPLA2-IIA; bactericidal activity against B. anthracis was detected in a high percentage of these samples. This anthracidal activity was correlated to the levels of sPLA2-IIA and was abolished by an sPLA2-IIA inhibitor. These results suggest that sPLA2-IIA may play a role in innate host defense against B. anthracis infection and that lethal toxin may help the bacteria to escape from the bactericidal action of sPLA2-IIA by inhibiting the production of this enzyme.

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“…In our previous study (18), we reported that Curosurf inhibits the synthesis of sPLA2-II by guinea pig AM but the mechanisms involved in this inhibition have not been elucidated. Here, we report that AS, which is composed only of phospholipids, reproduced the inhibitory effect of Curosurf although less effectively than the latter.…”

Section: Discussionmentioning

confidence: 96%

“…We have previously shown that Curosurf, which contains essentially phospholipids, inhibits the synthesis of sPLA2-II by AM (18). To examine whether phospholipids play a role in this process, we investigated the effect of a protein-free AS on the synthesis of sPLA2-II by AM.…”

Section: Effect Of Curosurf and As On Spla2-ii Expression By Ammentioning

confidence: 99%

“…We have recently reported that Curosurf inhibits the expression of the proinflammatory sPLA2-II by guinea-pig AM (18), but the mechanism involved in this inhibition has not been elucidated. Here, we show that phospholipid components of surfactant, mainly dioleylphosphatidylglycerol (DOPG), downregulate the expression of sPLA2-II in guinea-pig AM and that this effect occurs, at least in part, through the inhibition of TNF-␣ secretion.…”

mentioning

confidence: 99%

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Dioleylphosphatidylglycerol Inhibits the Expression of Type II Phospholipase A2 in Macrophages

Berger

Havet²,

Vial³

et al. 1999

Am J Respir Crit Care Med

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We have recently shown that modified natural pulmonary surfactant Curosurf inhibits the synthesis of type II phospholipase A2 (sPLA2-II) by cultured guinea-pig alveolar macrophages (AM). The goal of the present study was to identify the surfactant components and the mechanisms involved in this process. We show that protein-free artificial surfactant (AS) mimicked the inhibitory effect of Curosurf, suggesting that phospholipid components of surfactant play a role in the inhibition of sPLA2-II expression. Among surfactant phospholipids, dioleylphosphatidylglycerol (DOPG) was the most effective in inhibiting the synthesis of sPLA2-II. By contrast, the concentrations of platelet-activating factor (PAF)-acetylhydrolase and lysophospholipase activities remained unchanged, indicating that inhibition of sPLA2-II synthesis was caused by a specific effect of surfactant. The effect of DOPG on sPLA2-II synthesis was concentration-dependent and was accompanied by a rapid and time-dependent uptake of DOPG by AM whereas dipalmitoylphosphatidylcholine (DPPC) was only marginally taken up. Curosurf, AS, and DOPG inhibited tumor necrosis factor-alpha (TNF-alpha) secretion, a key step in the induction of sPLA2-II synthesis by AM, in contrast to DPPC which had only a marginal effect. We conclude that phospholipid components, especially DOPG, play a major role in the inhibition of sPLA2-II synthesis by surfactant and that this effect can be explained, at least in part, by an impairment of TNF-alpha secretion.

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Inhibition by pulmonary surfactant Curosurf of secretory phospholipase A2 expression in guinea-pig alveolar macrophages

Cited by 11 publications

References 10 publications

Pulmonary Secretory Phospholipase A<sub>2</sub> in Infants with Respiratory Distress Syndrome Stimulates in vitro Neutrophil Migration

Pulmonary Secretory Phospholipase A<sub>2</sub> in Infants with Respiratory Distress Syndrome Stimulates in vitro Neutrophil Migration

High Bactericidal Efficiency of Type IIA Phospholipase A2 against Bacillus anthracis and Inhibition of Its Secretion by the Lethal Toxin

Dioleylphosphatidylglycerol Inhibits the Expression of Type II Phospholipase A2 in Macrophages

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