Lyso-phospholipids exert a major injurious effect on lung cell membranes during Acute Respiratory Distress Syndrome (ARDS), but the mechanisms leading to their in vivo generation are still unknown. Intratracheal administration of LPS to guinea pigs induced the secretion of type II secretory phospholipase A2 (sPLA2-II) accompanied by a marked increase in fatty acid and lyso-phosphatidylcholine (lyso-PC) levels in the bronchoalveolar lavage fluid (BALF). Administration of LY311727, a specific sPLA2-II inhibitor, reduced by 60% the mass of free fatty acid and lyso-PC content in BALF. Gas chromatography/mass spectrometry analysis revealed that palmitic acid and palmitoyl-2-lyso-PC were the predominant lipid derivatives released in BALF. A similar pattern was observed after the intratracheal administration of recombinant guinea pig (r-GP) sPLA2-II and was accompanied by a 50-60% loss of surfactant phospholipid content, suggesting that surfactant is a major lung target of sPLA2-II. In confirmation, r-GP sPLA2-II was able to hydrolyze surfactant phospholipids in vitro. This hydrolysis was inhibited by surfactant protein A (SP-A) through a direct and selective protein-protein interaction between SP-A and sPLA2-II. Hence, our study reports an in vivo direct causal relationship between sPLA2-II and early surfactant degradation and a new process of regulation for sPLA2-II activity. Anti-sPLA2-II strategy may represent a novel therapeutic approach in lung injury, such as ARDS.
L Arbibe, K Koumanov, D Vial, C Rougeot, G Faure, N Havet, S Longacre, B B Vargaftig, G Béréziat, D R Voelker, C Wolf, L Touqui
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Identification of a Soluble Form Phospholipase A 2 Receptor as a Circulating Endogenous Inhibitor for Secretory Phospholipase A 2
K Higashino, Y Yokota, T Ono, S Kamitani, H Arita, K Hanasaki |
The Journal of biological chemistry | 2002 |
Effect of surfactant on pulmonary expression of type IIA PLA 2 in an animal model of acute lung injury
Y Wu, M Singer, F Thouron, M Alaoui-El-Azher, L Touqui |
American journal of physiology. Lung cellular and molecular physiology | 2002 |
Arachidonic Acid Differentially Affects Basal and Lipopolysaccharide-Induced sPLA 2 -IIA Expression in Alveolar Macrophages through NF-κB and PPAR-γ–Dependent Pathways
M Alaoui-El-Azher, Y Wu, N Havet, A Israël, A Lilienbaum, L Touqui |
Molecular pharmacology | 2002 |
The Influence of Lysophosphatidic Acid on the Functions of Human Dendritic Cells
E Panther, M Idzko, S Corinti, D Ferrari, Y Herouy, M Mockenhaupt, S Dichmann, P Gebicke-Haerter, FD Virgilio, G Girolomoni, J Norgauer |
Journal of immunology (Baltimore, Md. : 1950) | 2002 |
Therapeutic time-window of a group IIA phospholipase A2 inhibitor in rabbit acute lung injury: Correlation with lung surfactant protection
S Furue, K Mikawa, K Nishina, M Shiga, M Ueno, Y Tomita, K Kuwabara, I Teshirogi, T Ono, Y Hori, A Matsukawa, M Yoshinaga, H Obara |
Critical Care Medicine | 2001 |
Analysis of pulmonary surfactant by Fourier-transform infrared spectroscopy following exposure to Stachybotrys chartarum (atra) spores
KC McCrae, T Rand, RA Shaw, C Mason, MR Oulton, C Hastings, T Cherlet, JA Thliveris, HH Mantsch, J MacDonald, JE Scott |
Chemistry and Physics of Lipids | 2001 |
Effect of methylprednisolone on phospholipase A2 activity and lung surfactant degradation in acute lung injury in rabbits
K Kuwabara, S Furue, Y Tomita, M Ueno, T Ono, A Matsukawa, M Yoshinaga, K Mikawa, K Nishina, M Shiga, H Obara, Y Hori |
European Journal of Pharmacology | 2001 |
Phospholipase A2 is present in meconium and inhibits the activity of pulmonary surfactant: an in vitro study
AJ Schrama, AJ Beaufort, YR Sukul, SM Jansen, BJ Poorthuis, HM Berger |
Acta Pdiatrica | 2001 |
Meconium aspiration syndrome: a role for phospholipase A2 in the pathogenesis?
P Kääpä |
Acta Pdiatrica | 2001 |
Role of gut flora on intestinal group II phospholipase A 2 activity and intestinal injury in shock
RA Rozenfeld, X Liu, I Deplaen, W Hsueh |
AJP Gastrointestinal and Liver Physiology | 2001 |
Inhibition by unsaturated fatty acids of type II secretory phospholipase A2 synthesis in guinea-pig alveolar macrophages
MA el Azher, N Havet, M Singer, C Dumarey, L Touqui |
European Journal of Biochemistry | 2000 |
Pulmonary surfactant in innate immunity and the pathogenesis of tuberculosis
JS Ferguson, LS Schlesinger |
Tubercle and Lung Disease | 2000 |
Phospholipase A2 sécrétée de type IIA et syndrome inflammatoire
O Fourcade, MF Simon, FL Balle, J Fauvel, M Génestal, B Cathala, H Chap |
Réanimation Urgences | 2000 |
Polymer-Surfactant Treatment of Meconium-induced Acute Lung Injury
KW Lu, H William Taeusch, B Robertson, J Goerke, JA Clements |
American journal of respiratory and critical care medicine | 2000 |
Structures, Enzymatic Properties, and Expression of Novel Human and Mouse Secretory Phospholipase A 2 s
N Suzuki, J Ishizaki, Y Yokota, K Higashino, T Ono, M Ikeda, N Fujii, K Kawamoto, K Hanasaki |
The Journal of biological chemistry | 2000 |
Increasing molecular diversity of secreted phospholipases A2 and their receptors and binding proteins
E Valentin, G Lambeau |
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | 2000 |
Secretory Phospholipase A 2 Receptor-Mediated Activation of Cytosolic Phospholipase A 2 in Murine Bone Marrow-Derived Mast Cells
AN Fonteh, G Atsumi, T LaPorte, FH Chilton |
Journal of immunology (Baltimore, Md. : 1950) | 2000 |
Survey of the 1998 optical biosensor literature
DG Myszka |
Journal of Molecular Recognition | 1999 |
Human Meconium Has High Phospholipase A2 Activity and Induces Cellular Injury and Apoptosis in Piglet Lungs
R Holopainen, H Aho, J Laine, H Peuravuori, H Soukka, P Kääpä |
Pediatric Research | 1999 |
A role for phospholipase A2 in ARDS pathogenesis
L Touqui, L Arbibe |
Molecular Medicine Today | 1999 |
Dioleylphosphatidylglycerol Inhibits the Expression of Type II Phospholipase A2 in Macrophages
A Berger, N Havet, D Vial, L Arbibe, C Dumarey, ML Watson, L Touqui |
American journal of respiratory and critical care medicine | 1999 |
Functional Association of Type IIA Secretory Phospholipase A 2 with the Glycosylphosphatidylinositol-anchored Heparan Sulfate Proteoglycan in the Cyclooxygenase-2-mediated Delayed Prostanoid-biosynthetic Pathway
M Murakami, T Kambe, S Shimbara, S Yamamoto, H Kuwata, I Kudo |
The Journal of biological chemistry | 1999 |