Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome.

Gregory, T J; Longmore, William J.; Moxley, Michael A.; Whitsett, Jeffrey A.; Reed, Cynthia R.; Fowler, Alpha A.; Hudson, Leonard D.; Maunder, Richard J.; Crim, Courtney; Hyers, Thomas M.

doi:10.1172/jci115523

Cited by 608 publications

(396 citation statements)

References 33 publications

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“…This finding is consistent with findings that sPLA 2 -IIA is Ͼ100-fold more active on anionic, rather than zwitterionic, phospholipids (9,30). Remarkably, hydrolysis of PG occurs as early as 1 h after sPLA 2 -IIA administration, indicating that this enzyme could account for surfactant abnormalities observed at early phases in ARDS (17). In fact, alterations in the relative composition of the surfactant phospholipids are seen in patients with ARDS (17,18,43,44).…”

Section: Discussionsupporting

confidence: 89%

“…Our results may have important pathophysiological relevance, as patients with ARDS have elevated sPLA 2 activity and decreased SP-A concentrations in their BALF (17)(18)(19). However, no direct causal relationship has been demonstrated between the alteration in SP-A levels and the acute destruction of surfactant phospholipids.…”

Section: Discussionmentioning

confidence: 69%

“…Remarkably, hydrolysis of PG occurs as early as 1 h after sPLA 2 -IIA administration, indicating that this enzyme could account for surfactant abnormalities observed at early phases in ARDS (17). In fact, alterations in the relative composition of the surfactant phospholipids are seen in patients with ARDS (17,18,43,44). A decrease in PG levels (by Ͼ80% in three of these studies) and a moderate reduction of PC levels were observed.…”

Section: Discussionmentioning

confidence: 74%

“…SP-A, which is a member of the C-type lectin superfamily and contains a COOH-terminal carbohydrate recognition domain (CRD) (16), plays an important role in pulmonary host defense and seems to inhibit inflammation following lung infection. Decreased SP-A levels in BALF are observed in patients with ARDS or at risk of developing ARDS (17)(18)(19). Thus, increased sPLA 2 activity associated with decreased SP-A might promote the hydrolysis of pulmonary surfactant observed in ARDS.…”

Section: Inhibitory Effects Of Surfactant Protein a On Surfactant Phomentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 74%

Section: Inhibitory Effects Of Surfactant Protein a On Surfactant Phomentioning

confidence: 99%

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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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“…a lveolar surfactant is essential for lung stability and its composition and functional state are altered during pneumonia and acute respiratory distress syndrome (1,2). Pulmonary surfactant also plays an important role on the innate immune system by enhancing pathogen clearance and by regulating immune-cell functions (3).…”

mentioning

confidence: 99%

Surfactant protein B and A concentrations are increased in neonatal pneumonia

et al. 2015

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Background: Term newborns with pneumonia show a reduced pulmonary compliance due to multiple and illdefined factors. Surfactant proteins' (SPs) changes could have a role in the reduced compliance but the matter is still unsettled. The aim of this study was to clarify the meaning of SPs changes during pneumonia in term newborns. Methods: In 28 term ventilated newborns, 13 with pneumonia and 15 with no lung disease, we measured SP-B, SP-A, disaturated-phosphatidylcholine (DSPC), and total phospholipids (PL) concentrations in tracheal aspirates at intubation and close to extubation. We also measured DSPC kinetics using (U-13 C-PA)dipalmitoyl-phosphatidylcholine. results: At baseline, SP-B, expressed as % of PL, was significantly different between the groups, being 3.5-fold higher in pneumonia than controls. Conversely, SP-A did not vary between the groups. At extubation, SP-B and SP-A concentrations had decreased significantly in newborns with pneumonia, while there was no significant change in controls. DSPC t 1/2 was significantly shorter in the pneumonia group (11.8 (5.5-19.8) h vs. 26.6 (19.3-63.6) h, P = 0.011). conclusion: In term newborns with pneumonia, SP-B increases with respect to PL, and DSPC is turned over at a faster rate. Disease's resolution is associated with the restoration of the normal ratio between SP-B and PL.

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Both Prostaglandin E2 and Nitric Oxide Sequentially Mediate the Tumor Necrosis Factor α–Induced Inhibition of Surfactant Synthesis by Human Type II Pneumocytes

Vara

Arias-Dı́az²,

Garcı́a³

et al. 1995

Arch Surg

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Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome.

Cited by 608 publications

References 33 publications

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

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

Surfactant protein B and A concentrations are increased in neonatal pneumonia

Both Prostaglandin E2 and Nitric Oxide Sequentially Mediate the Tumor Necrosis Factor α–Induced Inhibition of Surfactant Synthesis by Human Type II Pneumocytes

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