Inhibitory effects of surfactant protein A on surfactant phospholipid hydrolysis by secreted phospholipases A2.

Abstract

Hydrolysis of surfactant phospholipids by secreted phospholipases A(2) (sPLA(2)) contributes to surfactant dysfunction in acute respiratory distress syndrome. The present study demonstrates that sPLA(2)-IIA, sPLA(2)-V, and sPLA(2)-X efficiently hydrolyze surfactant phospholipids in vitro. In contrast, sPLA(2)-IIC, -IID, -IIE, and -IIF have no effect. Since purified surfactant protein A (SP-A) has been shown to inhibit sPLA(2)-IIA activity, we investigated the in vitro effect of SP-A on the other active sPLA(2) and the consequences of sPLA(2)-IIA inhibition by SP-A on surfactant phospholipid hydrolysis. SP-A inhibits sPLA(2)-X activity, but fails to interfere with that of sPLA(2)-V. Moreover, in vitro inhibition of sPLA(2)-IIA-induces surfactant phospholipid hydrolysis correlates with the concentration of SP-A in surfactant. Intratracheal administration of sPLA(2)-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 sPLA(2)-IIA activity. Administration of sPLA(2)-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 sPLA(2) activity, which may play a protective role by maintaining surfactant integrity during lung injury.

• Authors: Sophie Chabot, Kamen Koumanov, Gérard Lambeau, Michael H Gelb, Viviane Balloy, Michel Chignard, Jeffrey A Whitsett, Lhousseine Touqui
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 171 Issue 2 Pg. 995-1000 (Jul 15 2003) ISSN: 0022-1767 [Print] United States
• PMID: 12847272 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Phosphatidylcholines
• Phosphatidylglycerols
• Phospholipids
• Pulmonary Surfactant-Associated Protein A
• Phospholipases A
• Group II Phospholipases A2

Topics

• Airway Resistance (genetics, physiology)
• Animals
• Electrophoresis, Polyacrylamide Gel
• Group II Phospholipases A2
• Hydrolysis
• Immunoblotting
• Intubation, Intratracheal
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Phosphatidylcholines (metabolism)
• Phosphatidylglycerols (antagonists & inhibitors, metabolism)
• Phospholipases A (administration & dosage, antagonists & inhibitors, metabolism, physiology)
• Phospholipids (analysis, antagonists & inhibitors, metabolism, physiology)
• Pulmonary Surfactant-Associated Protein A (deficiency, genetics, metabolism, physiology)
• Respiratory Distress Syndrome (enzymology, genetics, physiopathology, prevention & control)