A role for phospholipase A2 in ARDS pathogenesis

Touqui, Lhousseine; Arbibe, Laurence

doi:10.1016/s1357-4310(99)01470-7

Cited by 124 publications

(123 citation statements)

References 44 publications

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“…However, synthetic ether-linked lipids are now available that have direct structural analogy to lung surfactant lipids plus designed molecular behavior that enhances adsorption and spreading while maintaining very high dynamic surface tension lowering in surface films (e.g., [71,[205][206][207][208][209][210][211]). Moreover, such lipids have structural features making them resistant to phospholipases such as phospholipase A 2 , which has been implicated in the pathology of ALI/ARDS [65,[212][213][214][215][216][217][218]. Phospholipase-induced degradation of lung surfactant glycerophospholipids not only reduces the concentration of active components, but also generates reaction products such as lysophosphatidylcholine and fluid free fatty acids that can further decrease surface activity by interacting biophysically with remaining surfactant at the alveolar interface [55,59,70].…”

Section: Examples Of Research On New Synthetic Exogenous Surfactamentioning

confidence: 99%

Surfactant for Pediatric Acute Lung Injury

Willson¹,

Chess²,

Notter³

2008

Pediatric Clinics of North America

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SynopsisThis article reviews exogenous surfactant therapy and its use in mitigating acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in infants, children, and adults. Biophysical and animal research documenting surfactant dysfunction in ALI/ARDS is described, and the scientific rationale for treatment with exogenous surfactant is discussed. Major emphasis is on reviewing clinical studies of surfactant therapy in pediatric and adult patients with ALI/ARDS. Particular advantages from surfactant therapy in direct pulmonary forms of these syndromes are described. Also discussed are additional factors affecting the efficacy of exogenous surfactants in ALI/ARDS, including the multifaceted pathology of inflammatory lung injury, the effectiveness of surfactant delivery in injured lungs, and composition-based activity differences among clinical exogenous surfactant preparations.

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Section: Examples Of Research On New Synthetic Exogenous Surfactamentioning

confidence: 99%

Surfactant for Pediatric Acute Lung Injury

Willson¹,

Chess²,

Notter³

2008

Pediatric Clinics of North America

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“…The role of secreted phospholipases A 2 (sPLA 2 s) in a variety of inflammatory diseases including ARDS is now clearly established (3,4). The sPLA 2 s form a growing family of enzymes that catalyze the hydrolysis of the sn-2 ester bond of glycerophospholipids, leading to the production of free fatty acids and lysophospholipids that serve as precursors for a variety of lipid-derived mediators involved in numerous biological activities (5,6).…”

Section: Inhibitory Effects Of Surfactant Protein a On Surfactant Phomentioning

confidence: 99%

Inhibitory Effects of Surfactant Protein A on Surfactant Phospholipid Hydrolysis by Secreted Phospholipases A2

Chabot

Koumanov

Lambeau

et al. 2003

The Journal of Immunology

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Hydrolysis of surfactant phospholipids by secreted phospholipases A2 (sPLA2) contributes to surfactant dysfunction in acute respiratory distress syndrome. The present study demonstrates that sPLA2-IIA, sPLA2-V, and sPLA2-X efficiently hydrolyze surfactant phospholipids in vitro. In contrast, sPLA2-IIC, -IID, -IIE, and -IIF have no effect. Since purified surfactant protein A (SP-A) has been shown to inhibit sPLA2-IIA activity, we investigated the in vitro effect of SP-A on the other active sPLA2 and the consequences of sPLA2-IIA inhibition by SP-A on surfactant phospholipid hydrolysis. SP-A inhibits sPLA2-X activity, but fails to interfere with that of sPLA2-V. Moreover, in vitro inhibition of sPLA2-IIA-induces surfactant phospholipid hydrolysis correlates with the concentration of SP-A in surfactant. Intratracheal administration of sPLA2-IIA to mice causes hydrolysis of surfactant phosphatidylglycerol. Interestingly, such hydrolysis is significantly higher for SP-A gene-targeted mice, showing the in vivo inhibitory effect of SP-A on sPLA2-IIA activity. Administration of sPLA2-IIA also induces respiratory distress, which is more pronounced in SP-A gene-targeted mice than in wild-type mice. We conclude that SP-A inhibits sPLA2 activity, which may play a protective role by maintaining surfactant integrity during lung injury.

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“…23 In adults with ARDS, sPLA 2 activity in blood and lungs is increased and surfactant phospholipids are destroyed. 9,10 In this study, plasma sPLA 2 activity was positively correlated with duration of oxygen supplementation and significantly increased in infants with RDS, whereas no correlation with development of BPD was found. Possibly infants with the highest sPLA 2 activity in plasma had high pulmonary sPLA 2 activity as well, resulting in RDS due to surfactant phospholipid hydrolysis.…”

Section: Discussionmentioning

confidence: 45%

“…sPLA 2 can destroy bacteria through hydrolysis of their membrane lipids, and disturb surfactant function through hydrolysis of their phospholipid bilayer. 8,10,11 In adults, sPLA 2 is proposed as a sensitive marker for sepsis, and increased plasma levels of sPLA 2 are associated with development of multiple organ failure, vascular dilatation during shock and death. 6,7,12 The role of sPLA 2 in neonatal sepsis is unknown and its levels and relationship with well-recognized markers of inflammation have not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Secretory phospholipase A2 in newborn infants with sepsis

et al. 2008

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Objective: To investigate secretory phospholipase A 2 (sPLA 2 ) activity in neonatal sepsis.Study Design: Plasma sPLA 2 activity, C-reactive protein (CRP) concentration, leukocyte count and immature/total neutrophil (I/T) ratio were assessed in a group of 156 infants admitted for neonatal intensive care, who were classified as documented sepsis (n ¼ 24), suspected infection (n ¼ 77) and controls (n ¼ 55). Interleukin-6 (IL-6) concentrations were assessed in a subgroup (n ¼ 29).Result: sPLA 2 activity, CRP concentration and I/T ratio were higher in sepsis than in suspected infection or control groups. sPLA 2 activity advanced with increasing CRP, I/T ratio and IL-6 was highest in infants with respiratory distress syndrome (RDS). Compared to CRP, sPLA 2 had equal sensitivity and lower specificity. Compared to I/T ratio, sensitivity and specificity of sPLA 2 were higher.Conclusion: Plasma sPLA 2 activity is increased in neonatal sepsis and highest in infants with RDS. Further studies should assess the potential of sPLA 2 inhibition in neonatal sepsis.

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A role for phospholipase A2 in ARDS pathogenesis

Cited by 124 publications

References 44 publications

Surfactant for Pediatric Acute Lung Injury

Surfactant for Pediatric Acute Lung Injury

Inhibitory Effects of Surfactant Protein A on Surfactant Phospholipid Hydrolysis by Secreted Phospholipases A2

Secretory phospholipase A2 in newborn infants with sepsis

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