title: 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.affiliation: Unité de Défense Innée et Inflammation, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale E 336, Paris, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Chabot
authors.forename: Kamen
authors.initials: K
authors.lastname: Koumanov
authors.forename: Gérard
authors.initials: G
authors.lastname: Lambeau
authors.forename: Michael H
authors.initials: MH
authors.lastname: Gelb
authors.forename: Viviane
authors.initials: V
authors.lastname: Balloy
authors.forename: Michel
authors.initials: M
authors.lastname: Chignard
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Whitsett
authors.forename: Lhousseine
authors.initials: L
authors.lastname: Touqui
mesh_terms: D000403:Airway Resistance / Q000235:genetics / Q000502:physiology; D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D054501:Group II Phospholipases A2; D006868:Hydrolysis; D015151:Immunoblotting; D007442:Intubation, Intratracheal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010713:Phosphatidylcholines / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000037:antagonists & inhibitors / Q000378:metabolism; D010741:Phospholipases A / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D010743:Phospholipids / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000502:physiology; D037662:Pulmonary Surfactant-Associated Protein A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012128:Respiratory Distress Syndrome / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D010743:Phospholipids; D037662:Pulmonary Surfactant-Associated Protein A; D010741:Phospholipases A; D054501:Group II Phospholipases A2